This article references 51 other publications.

1. 1

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   In situ polymerizable polyethyleneglycol containing polyester polyol acrylates for tissue sealant applications

   Nivasu, Venkata M.; Reddy, Thimma T.; Tammishetti, Shekharam

   Biomaterials (2004), 25 (16), 3283-3291CODEN: BIMADU; ISSN:0142-9612. (Elsevier Science Ltd.)

   Polyesterpolyol macromers were prepd. with succinic acid and polyethylene glycols (PEG) of different mol. wts. The resulting polyols were acrylated to render them photo-cross-linkable. They could be very rapidly cross-linked into non-tacky films with long-wavelength UV radiation. The resulting products were characterized by gel content, water equil. swell, cross-link d., Tg, tensile strength, degrdn. and in vitro burst strengths. Though all of them formed transparent contact lens like films, increasing the PEG mol. wt. has resulted in polymers with higher hydrophilicity resulting in higher swelling, faster degrdn., higher tensile strength, elongation at break and burst strength. Addn. of vinyl pyrrolidinone as a reactive diluent has increased the mech. as well as burst strength of the polymer. In vitro release of sulfamethoxazole entrapped in these cross-linked matrixes was also studied.

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2. 2

   Hoshi, S.; Okamoto, F.; Arai, M.; Hirose, T.; Sugiura, Y.; Kaji, Y.; Oshika, T. In Vivo and In Vitro Feasibility Studies of Intraocular Use of Polyethylene Glycol-Based Synthetic Sealant to Close Retinal Breaks in Porcine and Rabbit Eyes. Invest. Ophthalmol. Visual Sci. 2015, 56, 4705– 4711,  DOI: 10.1167/iovs.14-15349

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   Ferguson, R. E. H.; Rinker, B. The Use of Hydrogel Sealant on Flexor Tendon Repairs to Prevent Adhesion Formation. Ann. Plast. Surg. 2006, 56, 54– 58,  DOI: 10.1097/01.sap.0000181666.00492.0e

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   The use of a hydrogel sealant on flexor tendon repairs to prevent adhesion formation

   Ferguson, Robert E. H.; Rinker, Brian

   Annals of Plastic Surgery (2006), 56 (1), 54-58CODEN: APCSD4; ISSN:0148-7043. (Lippincott Williams & Wilkins)

   The prevention of peritendinous adhesions after zone II flexor tendon repair poses a significant challenge to hand surgeons. This study evaluates a hydrogel sealant (FocalSeal-L) as a barrier to peritendinous adhesion formation. The deep flexors of toes 2 through 4 were divided and repaired in 30 chickens. Chickens were randomized to tendon repair with (n = 15) or without (n = 15) FocalSeal-L. Each group was further randomized to have their tendons studied postoperatively at 3 (n = 10), 6 (n = 10), or 12 (n = 10) weeks. Histol. evaluation revealed decreased peritendinous adhesion formation in the FocalSeal-L group. Biomech. anal. demonstrated a decrease in work of flexion in the FocalSeal-L group that was most pronounced at 6 wk (P = 0.0020). There was no significant difference in breaking strength. Apparently, an effective barrier to peritendinous adhesion formation, this sealant system is easy to use, biocompatible, and bioresorbable. In addn., it is not bulky or restrictive to tendon glide.

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4. 4

   Torchiana, D. F. Polyethylene Glycol Based Synthetic Sealants: Potential Uses in Cardiac Surgery. J. Card. Surg. 2003, 18, 504– 506,  DOI: 10.1046/j.0886-0440.2003.00305.x

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   Polyethylene glycol based synthetic sealants: potential uses in cardiac surgery

   Torchiana David F

   Journal of cardiac surgery (2003), 18 (6), 504-6 ISSN:0886-0440.

   Focalseal is a polyethylene glycol based synthetic hydrogel. It is FDA approved as a sealant to limit airleak following pulmonary resection. In preclinical use, this type of sealant has also been shown to be effective as a hemostatic adjunct to prevent anastomotic bleeding and to seal other types of closure such as the dura, pancreatic stump, or open wounds. The sealant has two components, a primer and a sealant, and is applied in two steps and then polymerized by the application of a blue-green light (Fig. 1) (Genzyme Biosurgery, Inc. Cambridge, MA). The sealant does not bond covalently to tissue and is degraded by hydrolysis. This kind of sealant is flexible and nontoxic and has many intriguing possible applications as well as some mechanical properties that are essential to understand for safe use.

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   Wibroe, P. P.; Ahmadvand, D.; Oghabian, M. A.; Yaghmur, A.; Moghimi, S. M. An Integrated Assessment of Morphology, Size, and Complement Activation of the PEGylated Liposomal Doxorubicin Products Doxil®, Caelyx®, DOXOrubicin, and SinaDoxosome. J. Controlled Release 2016, 221, 1– 8,  DOI: 10.1016/j.jconrel.2015.11.021

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   An integrated assessment of morphology, size, and complement activation of the PEGylated liposomal doxorubicin products Doxil, Caelyx, DOXOrubicin, and SinaDoxosome

   Wibroe, Peter P.; Ahmadvand, Davoud; Oghabian, Mohammad Ali; Yaghmur, Anan; Moghimi, S. Moein

   Journal of Controlled Release (2016), 221 (), 1-8CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)

   In order to improve patient's benefit and safety, comprehensive regulatory guidelines on specificities of Non-Biol. Complex Drugs (NBCDs), such as doxorubicin-encapsulated liposomes, and their follow-on versions are needed. Here, we compare Doxil and its European analog Caelyx with the two follow-on products DOXOrubicin (approved by the US Food and Drug Administration) and SinaDoxosome (produced in Iran) by cryogenic transmission electron microscopy, dynamic light scattering and Nanoparticle Tracking Anal., and assess their potential in activating the complement system in human sera. We found subtle physicochem. differences between the tested liposomal products and even between the tested batches of Doxil and Caelyx. Notably, these included differences in vesicular population aspect ratios and particle no. Among the tested products, only SinaDoxosome, in addn. to the presence of unilamellar vesicles with entrapped doxorubicin crystals, contained empty circular disks. Differences were also found in complement responses, which may be related to some morphol. differences. This study has demonstrated an integrated biophys. and immunol. toolbox for improved anal. and detection of phys. differences among vesicular populations that may modulate their clin. performance. Combined, these approaches may help better product selection for infusion to the patients as well as for improved design and characterization of future vesicular NBCDs with enhanced clin. performance and safety.

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7. 7

   Koren, E.; Apte, A.; Jani, A.; Torchilin, V. P. Multifunctional PEGylated 2C5-Immunoliposomes Containing pH-Sensitive Bonds and TAT Peptide for Enhanced Tumor Cell Internalization and Cytotoxicity. J. Controlled Release 2012, 160, 264– 273,  DOI: 10.1016/j.jconrel.2011.12.002

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   Deng, Z. J.; Morton, S. W.; Ben-Akiva, E.; Dreaden, E. C.; Shopsowitz, K. E.; Hammond, P. T. Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment. ACS Nano 2013, 7, 9571– 9584,  DOI: 10.1021/nn4047925

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   Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment

   Deng, Zhou J.; Morton, Stephen W.; Ben-Akiva, Elana; Dreaden, Erik C.; Shopsowitz, Kevin E.; Hammond, Paula T.

   ACS Nano (2013), 7 (11), 9571-9584CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)

   A single nanoparticle platform has been developed through the modular and controlled layer-by-layer process to codeliver siRNA that knocks down a drug-resistance pathway in tumor cells and a chemotherapy drug to challenge a highly aggressive form of triple-neg. breast cancer. Layer-by-layer films were formed on nanoparticles by alternately depositing siRNA and poly-L-arginine; a single bilayer on the nanoparticle surface could effectively load up to 3500 siRNA mols., and the resulting LbL nanoparticles exhibit an extended serum half-life of 28 h. In animal models, one dose via i.v. administration significantly reduced the target gene expression in the tumors by almost 80̂. By generating the siRNA-loaded film atop a doxorubicin-loaded liposome, we identified an effective combination therapy with siRNA targeting multidrug resistance protein 1, which significantly enhanced doxorubicin efficacy by 4 fold in vitro and led to up to an 8-fold decrease in tumor vol. compared to the control treatments with no obsd. toxicity. The results indicate that the use of layer-by-layer films to modify a simple liposomal doxorubicin delivery construct with a synergistic siRNA can lead to significant tumor redn. in the cancers that are otherwise nonresponsive to treatment with Doxil or other common chemotherapy drugs. This approach provides a potential strategy to treat aggressive and resistant cancers, and a modular platform for a broad range of controlled multidrug therapies customizable to the cancer type in a singular nanoparticle delivery system.

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9. 9

   Aseyev, V.; Tenhu, H.; Winnik, F. M. Non-Ionic Thermoresponsive Polymers in Water. Adv. Polym. Sci. 2010, 242, 29– 89,  DOI: 10.1007/12_2010_57

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    Saeki, S.; Kuwahara, N.; Nakata, M.; Kaneko, M. Upper and Lower Critical Solution Temperatures in Poly(ethylene glycol) Solutions. Polymer 1976, 17, 685– 689,  DOI: 10.1016/0032-3861(76)90208-1

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    Upper and lower critical solution temperatures in poly(ethylene glycol) solutions

    Saeki, Susumu; Kuwahara, Nobuhiro; Nakata, Mitsuo; Kaneko, Motozo

    Polymer (1976), 17 (8), 685-9CODEN: POLMAG; ISSN:0032-3861.

    Upper and lower crit. soln. temps. were detd. for poly(ethylene glycol) [25322-68-3] (viscosity av. mol. wt. ‾Mη) = 2.18 to ∼1020 × 103) in tert-BuOAc and in H2O. For a sample of ‾Mη = 719 × 103 in tert-BuOAc the phase diagram had an hourglass shape whereas the phase diagram of a soln. of polymer o ‾Mη = 2.18 to ∼2.29 × 103 in H2O was of the closed loop type. The value of the pressure dependence of the lower crit. soln. temp. in the polymer (‾Mη 1020 × 103)-H2O system at 0 to ∼50 atm was negligibly small and pos.

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11. 11

    Lutz, J.-R. Polymerization of Oligo(Ethylene Glycol) (Meth)Acrylates: Toward New Generations of Smart Biocompatible Materials. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 3459– 3470,  DOI: 10.1002/pola.22706

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    Polymerization of oligo(ethylene glycol) (meth)acrylates: toward new generations of smart biocompatible materials

    Lutz, Jean-Francois

    Journal of Polymer Science, Part A: Polymer Chemistry (2008), 46 (11), 3459-3470CODEN: JPACEC; ISSN:0887-624X. (John Wiley & Sons, Inc.)

    A review. Monomers composed of a (meth)acrylate moiety connected to a short poly(ethylene)glycol (PEG) chain are versatile building-blocks for the prepn. of "smart" biorelevant materials. Many of these monomers are com. and can be easily polymd. by either anionic, free-radical, or controlled radical polymn. The latter approach allows synthesis of well-defined PEG-based macromol. architectures such as amphiphilic block copolymers, dense polymer brushes, or biohybrids. Furthermore, the resulting polymers exhibit fascinating soln. properties in aq. medium. Depending on the mol. structure of their monomer units, non linear PEG analogs can be either insol. in water, readily sol. up to 100°, or thermoresponsive. Thus, these polymers can be used for building a wide variety of modern materials such as biosensors, artificial tissues, smart gels for chromatog., and drug carriers.

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12. 12

    Lee, J.; McGrath, A. J.; Hawker, C. J.; Kim, B.-S. pH-Tunable Thermoresponsive PEO-Based Functional Polymers with Pendant Amine Groups. ACS Macro Lett. 2016, 5, 1391– 1396,  DOI: 10.1021/acsmacrolett.6b00830

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    12

    pH-Tunable Thermoresponsive PEO-Based Functional Polymers with Pendant Amine Groups

    Lee, Joonhee; McGrath, Alaina J.; Hawker, Craig J.; Kim, Byeong-Su

    ACS Macro Letters (2016), 5 (12), 1391-1396CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)

    Thermoresponsive polymers exhibiting lower crit. soln. temps. (LCSTs) in aq. soln. have garnered considerable attention for the development of smart materials. Herein, we report the synthesis and properties of pH-tunable thermoresponsive poly(ethylene oxide) (PEO)-based functional polymers bearing pendant amine groups with varying cloud points. Well-defined poly(ethylene oxide-co-allyl glycidyl ether) (P(EO-co-AGE)) copolymers were prepd. via controlled anionic ring-opening copolymn. of ethylene oxide (EO) with 10 mol % of a functional allyl glycidyl ether (AGE) comonomer. Facile, modular thiol-ene click chem. was then employed to introduce a library of different aminothiols as side chains to the initial P(EO-co-AGE) copolymer. Depending on the nature of the pendant amine groups (primary amine, dimethylamine, and diethylamine) and the hydrophobicity of the side chains (Et, Pr, and hexyl), the cloud points could be tuned from 44-100 °C under different pH conditions. This is the first systematic investigation into the effect of PEO copolymer side chains on cloud point, which opens up the opportunity to make new thermoresponsive polymers for a variety of smart material applications.

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13. 13

    Koda, Y.; Terashima, T.; Sawamoto, M. LCST-Type Phase Separation of Poly[poly(ethylene glycol) methyl ether methacrylate]s in Hydrofluorocarbon. ACS Macro Lett. 2015, 4, 1366– 1369,  DOI: 10.1021/acsmacrolett.5b00771

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    13

    LCST-Type Phase Separation of Poly[poly(ethylene glycol) methyl ether methacrylate]s in Hydrofluorocarbon

    Koda, Yuta; Terashima, Takaya; Sawamoto, Mitsuo

    ACS Macro Letters (2015), 4 (12), 1366-1369CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)

    Poly[poly(ethylene glycol) Me ether methacrylate]s [poly(PEGMA)s] sharply and reversibly exhibited lower crit. soln. temp. (LCST)-type phase sepn. in 2H,3H-perfluoropentane (2HPFP). The cloud points decreased from 52 to 41 °C with increasing the PEG pendant length [-(CH2CH2O)mCH3: m = 4.5, 9, 19]. The cloud point was precisely controlled via the addn. of perfluoroalkanes (e.g., perfluorooctane) to the 2HPFP soln.: typically, it was inversely proportional to the amt. of perfluorooctane in the mixt. The unique thermoresponsive soly. further afforded the temp.-mediated micellization of a block copolymer of PEG19MA and Me methacrylate (MMA) in 2HPFP to uniquely give a PEG-core micelle with PMMA shell. Therefore, the LCST phase sepn. properties in the hydrofluorocarbon would open new vistas for thermoresponsive polymeric materials.

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14. 14

    Koda, Y.; Terashima, T.; Sawamoto, M. Multimode Self-Folding Polymers via Reversible and Thermoresponsive Self-Assembly of Amphiphilic/Fluorous Random Copolymers. Macromolecules 2016, 49, 4534– 4543,  DOI: 10.1021/acs.macromol.6b00998

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    14

    Multimode Self-Folding Polymers via Reversible and Thermoresponsive Self-Assembly of Amphiphilic/Fluorous Random Copolymers

    Koda, Yuta; Terashima, Takaya; Sawamoto, Mitsuo

    Macromolecules (Washington, DC, United States) (2016), 49 (12), 4534-4543CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)

    Multimode self-folding polymers were created via the reversible and thermoresponsive self-assembly of amphiphilic/fluorous random copolymers bearing poly(ethylene glycol) (PEG) and perfluoroalkyl pendants in water, N,N-dimethylformamide (DMF), and 2H,3H-perfluoropentane (2HPFP). The random copolymers with precision primary structure were synthesized by ruthenium-catalyzed living radical copolymn. of PEG Me ether methacrylates and perfluoroalkyl methacrylates. Owing to three distinct properties of the hydrophobic backbone, hydrophilic PEG chains, and fluorous perfluorinated pendants, the random copolymers allowed various self-assembly modes for different folded structures by changing solvents. Namely, they form self-folding polymers of fluorous and/or hydrophobic cores in water or DMF, while they in turn provide reverse self-folding polymers of hydrophilic PEG cores in 2HPFP. The reverse folding in 2HPFP was further promoted by lower crit. soln. temp.-type phase sepn. of the PEG units upon heating.

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15. 15

    Elsabahy, M.; Heo, G. S.; Lim, S.-M.; Sun, G.; Wooley, K. L. Polymeric Nanostructures for Imaging and Therapy. Chem. Rev. 2015, 115, 10967– 11011,  DOI: 10.1021/acs.chemrev.5b00135

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    Polymeric Nanostructures for Imaging and Therapy

    Elsabahy, Mahmoud; Heo, Gyu Seong; Lim, Soon-Mi; Sun, Guorong; Wooley, Karen L.

    Chemical Reviews (Washington, DC, United States) (2015), 115 (19), 10967-11011CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)

    A review. This review will focus on several recent advances in the design of polymeric nanoparticles that have been utilized for delivery of diagnostic and/or therapeutic agents, as well as the various barriers toward the clin. development of these materials. After a brief overview of the capabilities and challenges with medical imaging and therapy, in general, disease-specific examples of polymer nanoparticles designed specially to overcome the challenges and address unmet medical needs will be discussed in detail.

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16. 16

    Fernandez-Trillo, F.; Grover, L. M.; Stephenson-Brown, A.; Harrison, P.; Mendes, P. M. Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles. Angew. Chem., Int. Ed. 2017, 56, 3142– 3160,  DOI: 10.1002/anie.201607825

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    16

    Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles

    Fernandez-Trillo, Francisco; Grover, Liam M.; Stephenson-Brown, Alex; Harrison, Paul; Mendes, Paula M.

    Angewandte Chemie, International Edition (2017), 56 (12), 3142-3160CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)

    A review. The important role of vesicles in many aspects of cell function is well-recognized, but only recently have sophisticated imaging techniques begun to reveal their ubiquity in nature. While we further our understanding of the biol. properties of vesicles and their physiol. functions, increasingly elegant artificial vesicles are being developed for a wide range of technol. applications and basic research. Herein, we examine the state of the art of biol. and synthetic vesicles and place their biol. features in the context of recent synthetic developments, thus providing a unique overview of these complex and rapidly developing fields. The challenges and opportunities assocd. with future biol. and synthetic studies of vesicles are also presented.

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17. 17

    Hussain, H.; Mya, K. Y.; He, C. Self-Assembly of Brush-Like Poly[poly(ethylene glycol) methyl ether methacrylate] Synthesized via Aqueous Atom Transfer Radical Polymerization. Langmuir 2008, 24, 13279– 13286,  DOI: 10.1021/la802734e

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    17

    Self-Assembly of Brush-Like Poly[poly(ethylene glycol) methyl ether methacrylate] Synthesized via Aqueous Atom Transfer Radical Polymerization

    Hussain, Hazrat; Mya, Khine Yi; He, Chaobin

    Langmuir (2008), 24 (23), 13279-13286CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)

    Self-assembly of brush-like well-defined poly[poly(ethylene glycol) Me ether methacrylate] homopolymers, abbreviated as P(PEGMA-475) and P(PEGMA-1100) is investigated in aq. soln. by employing dynamic/static light scattering (DLS/SLS) and transmission electron microscopy (TEM), whereas 475 and 1100 is molar mass of the resp. PEGMA macromonomer. The mentioned brush-like homopolymers are synthesized by aq. ATRP at room temp. The crit. assocn. concn. (CAC) of the synthesized polymers in water depends on the length of the PEG side chains but not on the overall molar mass of the polymer. Thus, approx. the same CAC of ∼0.35 mg/mL is estd. for various P(PEGMA-1100) samples, and ∼0.7 mg/mL is estd. for P(PEGMA-475) series. All the investigated P(PEGMA-1100) samples form multimol. micelles in aq. soln., where the hydrodynamic size (Rh) and the aggregation no. (Nagg) of micelles decreases as the mol. wt. of P(PEGMA-1100) increases. This can be attributed to the increased steric hindrances between the PEG side chains in corona of micelles formed by higher molar mass P(PEGMA-1100). The tendency of micelle formation by samples of P(PEGMA-475) series is significantly lower than that of P(PEGMA-1100) series, as demonstrated by their significantly higher CAC and micelles of lower Nagg. The Rh of micelles does not depend strongly on polymer concn., which suggests that these micelles are formed via the closed assocn. model. Micelles formed by P(PEGMA-1100) series slightly shrink with increase in temp. from 25 to 60 °C, while those of P(PEGMA-475) series are found to be insensitive to the same temp. variation. Finally, TEM is carried out to visualize the formed micelles after transferring the aq. soln. to carbon film.

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18. 18

    Terashima, T. Functional Spaces in Star and Single-Chain Polymers via Living Radical Polymerization. Polym. J. 2014, 46, 664– 673,  DOI: 10.1038/pj.2014.57

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    18

    Functional spaces in star and single-chain polymers via living radical polymerization

    Terashima, Takaya

    Polymer Journal (Tokyo, Japan) (2014), 46 (10), 664-673CODEN: POLJB8; ISSN:0032-3896. (NPG Nature Asia-Pacific)

    A review. This article reviews recent advances in the creation of functional spaces with core-functionalized star polymers and single-chain folding/crosslinked polymers via living radical polymn. Various core-functionalized star polymers were efficiently prepd. with functional linking agents and monomers to perform unique functions. For example, they can serve as nanoreactors for active and robust catalysis in org. reactions and polymn. and as nanocapsules for selective and stimuli-responsive mol. recognition. Single-chain folding polymers were obtained from the self-folding of amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) chains and hydrophobic alkyl pendants in water, resulting in unimer micelles with dynamic hydrophobic domains. The folded structure could be further fixed via the intramol. crosslinking of the hydrophobic interior. In addn., cation template-assisted cyclopolymn. and concurrent tandem living radical polymn. with in situ monomer transesterification were also developed for the one-pot synthesis of cyclopolymers with large in-chain cavities and gradient and sequence-controlled copolymers.

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19. 19

    Koda, Y.; Terashima, T.; Sawamoto, M. Fluorous Microgel Star Polymers: Selective Recognition and Separation of Polyfluorinated Surfactants and Compounds in Water. J. Am. Chem. Soc. 2014, 136, 15742– 15748,  DOI: 10.1021/ja508818j

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    19

    Fluorous Microgel Star Polymers: Selective Recognition and Separation of Polyfluorinated Surfactants and Compounds in Water

    Koda, Yuta; Terashima, Takaya; Sawamoto, Mitsuo

    Journal of the American Chemical Society (2014), 136 (44), 15742-15748CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    Immiscible with either hydrophobic or hydrophilic solvents, polyfluorinated compds. (PFCs) are generally "fluorous", some of which have widely been employed as surfactants and water/oil repellents. Given the prevailing concern about the environmental pollution and the biocontamination by PFCs, their efficient removal and recycle from industrial wastewater and products are critically required. This paper demonstrates that fluorous-core star polymers consisting of a polyfluorinated microgel core and hydrophilic PEG-functionalized arms efficiently and selectively capture PFCs in water into the cores by fluorous interaction. For example, with over 10 000 fluorine atoms in the core and approx. 100 hydrophilic arms, the fluorous stars remove perfluorooctanoic acid (PFOA) and related PFCs in water from 10 ppm to as low as a ppb (ppb) level, or an over 98% removal. Dually functionalized microgel-core star polymers with perfluorinated alkanes and addnl. amino (or ammonium) groups cooperatively recognize PFOA or its ammonium salt and, in addn., release the guests upon external stimuli. The "smart" performance shows that the fluorous-core star polymers are promising PFC sepn., recovery, and recycle materials for water purifn. toward sustainable society.

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20. 20

    Koda, Y.; Terashima, T.; Sawamoto, M. Star Polymer Gels with Fluorinated Microgels via Star–Star Coupling and Cross-Linking for Water Purification. ACS Macro Lett. 2015, 4, 377– 380,  DOI: 10.1021/acsmacrolett.5b00127

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    20

    Star Polymer Gels with Fluorinated Microgels via Star-Star Coupling and Cross-Linking for Water Purification

    Koda, Yuta; Terashima, Takaya; Takenaka, Mikihito; Sawamoto, Mitsuo

    ACS Macro Letters (2015), 4 (4), 377-380CODEN: AMLCCD; ISSN:2161-1653. (American Chemical Society)

    Two types of star polymer gels contg. perfluorinated microgels were created as purifn. materials to sep. polyfluorinated surfactants (e.g., perfluorooctanoic acid) from water. One macrogel is prepd. by the radical coupling of fluorine and/or amine-functionalized microgel star polymers alone, while another is done by the radical crosslinking of the star polymers with poly(ethylene glycol) Me ether methacrylate. Importantly, the reactive olefin remaining within the microgel cores was directly employed for both coupling and crosslinking reactions. Swelling properties of star polymer gels were effectively controlled by the latter crosslinking technique. Analyzed by small-angle X-ray scattering, a star-star coupling gel typically consists of a three-dimensional network where star polymers are sequentially connected with the microgels at the const. interval of about 20 nm. Owing to the fluorous and acid/base cooperative interaction, star polymer gels carrying fluorine/amine-functionalized microgels efficiently captured polyfluorinated surfactants in water and successfully afforded the removal from water via simple mixing and filtration.

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21. 21

    Pelegri-O’Day, E. M.; Lin, E.-W.; Maynard, H. D. Therapeutic Protein–Polymer Conjugates: Advancing Beyond PEGylation. J. Am. Chem. Soc. 2014, 136, 14323– 14332,  DOI: 10.1021/ja504390x

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    21

    Therapeutic Protein-Polymer Conjugates: Advancing Beyond PEGylation

    Pelegri-O'Day, Emma M.; Lin, En-Wei; Maynard, Heather D.

    Journal of the American Chemical Society (2014), 136 (41), 14323-14332CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    A review. Protein-polymer conjugates are widely used as therapeutics. All Food and Drug Administration (FDA)-approved protein conjugates are covalently linked to poly(ethylene glycol) (PEG). These PEGylated drugs have longer half-lives in the bloodstream, leading to less frequent dosing, which is a significant advantage for patients. However, there are some potential drawbacks to PEG that are driving the development of alternatives. Polymers that display enhanced pharmacokinetic properties along with addnl. advantages such as improved stability or degradability will be important to advance the field of protein therapeutics. This perspective presents a summary of protein-PEG conjugates for therapeutic use and alternative technologies in various stages of development as well as suggestions for future directions. Established methods of producing protein-PEG conjugates and new approaches utilizing controlled radical polymn. are also covered.

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22. 22

    Krall, N.; Da Cruz, F. P.; Boutureira, O.; Bernardes, G. J. L. Site-Selective Protein-Modification Chemistry for Basic Biology and Drug Development. Nat. Chem. 2016, 8, 103– 113,  DOI: 10.1038/nchem.2393

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    22

    Site-selective protein-modification chemistry for basic biology and drug development

    Krall, Nikolaus; da Cruz, Filipa P.; Boutureira, Omar; Bernardes, Goncalo J. L.

    Nature Chemistry (2016), 8 (2), 103-113CODEN: NCAHBB; ISSN:1755-4330. (Nature Publishing Group)

    A review. Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-detd. sites. These reactions are now used to selectively install particular modifications on proteins for many biol. and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to det. their exact biol. roles. Labeling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiol. parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chem. site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.

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23. 23

    Koda, Y.; Terashima, T.; Sawamoto, M.; Maynard, H. D. Amphiphilic/Fluorous Random Copolymers as a New Class of Non-Cytotoxic Polymeric Materials for Protein Conjugation. Polym. Chem. 2015, 6, 240– 247,  DOI: 10.1039/C4PY01346H

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    23

    Amphiphilic/fluorous random copolymers as a new class of non-cytotoxic polymeric materials for protein conjugation

    Koda, Yuta; Terashima, Takaya; Sawamoto, Mitsuo; Maynard, Heather D.

    Polymer Chemistry (2015), 6 (2), 240-247CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)

    Herein, amphiphilic/fluorous random copolymers bearing poly(ethylene glycol) (PEG) chains and perfluorinated alkane pendants were developed as novel non-cytotoxic polymers for protein conjugation. Three kinds of random copolymers with different initiating terminals (carboxylic acid, pyridyl disulfide, and N-hydroxysuccinimide ester) were prepd. by reversible addn.-fragmentation chain transfer (RAFT) copolymn. of a PEG Me ether methacrylate and a perfluorinated alkane methacrylate with the corresponding functional chain transfer agents. All of the polymers were sol. in water to form nanostructures with perfluorinated compartments via fluorous interaction: large aggregates from the intermol. multi-chain assocn. and compact unimer micelles from the intramol. single-chain folding. Such a PEGylated and perfluorinated random copolymer was non-cytotoxic to NIH 3T3 mouse embryonic fibroblast cells and human umbilical vein endothelial cells (HUVECs). Addnl., a random copolymer with a pyridyl disulfide terminal was also successfully conjugated with a thiolated lysozyme.

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24. 24

    Koda, Y.; Terashima, T.; Maynard, H. D.; Sawamoto, M. Protein Storage with Perfluorinated PEG Compartments in a Hydrofluorocarbon Solvent. Polym. Chem. 2016, 7, 6694– 6698,  DOI: 10.1039/C6PY01333C

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    24

    Protein storage with perfluorinated PEG compartments in a hydrofluorocarbon solvent

    Koda, Yuta; Terashima, Takaya; Maynard, Heather D.; Sawamoto, Mitsuo

    Polymer Chemistry (2016), 7 (44), 6694-6698CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)

    We report a novel storage technol. of proteins with surface-perfluorinated poly(ethylene glycol) compartments in 2H,3H-perfluoropentane. The compartments were obtained from self-folding and self-assembly of an amphiphilic random copolymer bearing poly(ethylene glycol) and perfluoroalkyl pendants in the hydrofluorocarbon. Lysozyme and α-chymotrypsin as model proteins were efficiently encapsulated within the PEG compartments and quant. recovered therefrom with water. The recovered lysozyme maintained the original higher order structure without denaturation to show enzymic activity for the hydrolysis of Micrococcus lysodeikticus as high as its original counterpart in water. The storage technol. was further effective to inhibit inactivation of α-chymotrypsin.

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25. 25

    Matsumura, Y.; Maeda, H. A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs. Cancer Res. 1986, 46, 6387– 6392

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    A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs

    Matsumura, Yasuhiro; Maeda, Hiroshi

    Cancer Research (1986), 46 (12, Pt. 1), 6387-92CODEN: CNREA8; ISSN:0008-5472.

    A polymer conjugated to the anticancer protein neocarzinostatin, named smancs, (copolymer of styrene and maleic acid) was shown earlier to accumulate more in tumor tissues than did neocarzinostatin. To det. the general mechanism of this tumoritropic accumulation of smancs and other protein, radioactive (51Cr-labeled) proteins of various mol. sizes (Mr 12,000 to 160,00) and other properties were used. In addn., dye-complexed serum albumin was used to visualize the accumulation of proteins in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concn. in the tumor to that in the blood of 5 was obtained within 19-72 h. A large protein like IgG required a longer time to reach this value of 5. The protein concn. ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. The tumoritropic accumulation of these proteins apparently resulted because of the hypervasculature, an enhanced permeability to even macromols., and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromols. in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromols. from tumor tissue. The present finding is of potential value in macromol. tumor therapeutics and diagnosis.

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26. 26

    Fang, J.; Nakamura, H.; Maeda, H. The EPR Effect: Unique Features of Tumor Blood Vessels for Drug Delivery, Factors Involved, and Limitations and Augmentation of the Effect. Adv. Drug Delivery Rev. 2011, 63, 136– 151,  DOI: 10.1016/j.addr.2010.04.009

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    26

    The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect

    Fang, Jun; Nakamura, Hideaki; Maeda, Hiroshi

    Advanced Drug Delivery Reviews (2011), 63 (3), 136-151CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)

    A review. The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors related to their anatomical and pathophysiol. differences from normal tissues. For example, angiogenesis leads to high vascular d. in solid tumors, large gaps exist between endothelial cells in tumor blood vessels, and tumor tissues show selective extravasation and retention of macromol. drugs. This EPR effect served as a basis for development of macromol. anticancer therapy. We demonstrated methods to enhance this effect artificially in clin. settings. Of great importance was increasing systolic blood pressure via slow angiotensin II infusion. Another strategy involved utilization of NO-releasing agents such as topical nitroglycerin, which releases nitrite. Nitrite is converted to NO more selectively in the tumor tissues, which leads to a significantly increased EPR effect and enhanced antitumor drug effects as well. This review discusses mol. mechanisms of factors related to the EPR effect, the unique anatomy of tumor vessels, limitations and techniques to avoid such limitations, augmenting tumor drug delivery, and exptl. and clin. findings.

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27. 27

    Cabral, H.; Kataoka, K. Progress of Drug-Loaded Polymeric Micelles into Clinical Studies. J. Controlled Release 2014, 190, 465– 476,  DOI: 10.1016/j.jconrel.2014.06.042

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    27

    Progress of drug-loaded polymeric micelles into clinical studies

    Cabral, Horacio; Kataoka, Kazunori

    Journal of Controlled Release (2014), 190 (), 465-476CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)

    A review. Targeting tumors with long-circulating nano-scaled carriers is a promising strategy for systemic cancer treatment. Compared with free small therapeutic agents, nanocarriers can selectively accumulate in solid tumors through the enhanced permeability and retention (EPR) effect, which is characterized by leaky blood vessels and impaired lymphatic drainage in tumor tissues, and achieve superior therapeutic efficacy, while reducing side effects. In this way, drug-loaded polymeric micelles, i.e. self-assemblies of amphiphilic block copolymers consisting of a hydrophobic core as a drug reservoir and a poly(ethylene glycol) (PEG) hydrophilic shell, have demonstrated outstanding features as tumor-targeted nanocarriers with high translational potential, and several micelle formulations are currently under clin. evaluation. This review summarizes recent efforts in the development of these polymeric micelles and their performance in human studies, as well as our recent progress in polymeric micelles for the delivery of nucleic acids and imaging.

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28. 28

    Anraku, Y.; Kishimura, A.; Kamiya, M.; Tanaka, S.; Nomoto, T.; Toh, K.; Matsumoto, Y.; Fukushima, S.; Sueyoshi, D.; Kano, M. R.; Urano, Y.; Nishiyama, N.; Kataoka, K. Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors. Angew. Chem., Int. Ed. 2016, 55, 560– 565,  DOI: 10.1002/anie.201508339

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    28

    Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors

    Anraku, Yasutaka; Kishimura, Akihiro; Kamiya, Mako; Tanaka, Sayaka; Nomoto, Takahiro; Toh, Kazuko; Matsumoto, Yu; Fukushima, Shigeto; Sueyoshi, Daiki; Kano, Mitsunobu R.; Urano, Yasuteru; Nishiyama, Nobuhiro; Kataoka, Kazunori

    Angewandte Chemie, International Edition (2016), 55 (2), 560-565CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)

    The design and construction of nanoreactors are important for biomedical applications of enzymes, but lipid- and polymeric-vesicle-based nanoreactors have some practical limitations. We have succeeded in prepg. enzyme-loaded polyion complex vesicles (PICsomes) through a facile protein-loading method. The preservation of enzyme activity was confirmed even after crosslinking of the PICsomes. The cross-linked β-galactosidase-loaded PICsomes (β[email protected]) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER-βGal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4 days after administration of the β[email protected] Intravital confocal microscopy showed continuous prodn. of HMDER and its distribution throughout the tumor tissues. Thus, enzyme-loaded PICsomes are useful for prodrug activation at the tumor site and could be a versatile platform for enzyme delivery in enzyme prodrug therapy.

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29. 29

    Ouchi, M.; Terashima, T.; Sawamoto, M. Transition Metal-Catalyzed Living Radical Polymerization: Toward Perfection in Catalysis and Precision Polymer Synthesis. Chem. Rev. 2009, 109, 4963– 5050,  DOI: 10.1021/cr900234b

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    29

    Transition Metal-Catalyzed Living Radical Polymerization: Toward Perfection in Catalysis and Precision Polymer Synthesis

    Ouchi, Makoto; Terashima, Takaya; Sawamoto, Mitsuo

    Chemical Reviews (Washington, DC, United States) (2009), 109 (11), 4963-5050CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)

    A review. The review covers two chronol. periods: 1. 1994-2000 (460 refs.), 2 2001-2008 (970 refs.). The two periods were compared and major discoveries were summarized.

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30. 30

    Yoda, H.; Nakatani, K.; Terashima, T.; Ouchi, M.; Sawamoto, M. Ethanol-Mediated Living Radical Homo- and Copolymerizations with Cp*-Ruthenium Catalysts: Active, Robust, and Universal for Functionalized Methacrylates. Macromolecules 2010, 43, 5595– 5601,  DOI: 10.1021/ma100589b

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    30

    Ethanol-Mediated Living Radical Homo- and Copolymerizations with Cp*-Ruthenium Catalysts: Active, Robust, and Universal for Functionalized Methacrylates

    Yoda, Hiroaki; Nakatani, Kazuhiro; Terashima, Takaya; Ouchi, Makoto; Sawamoto, Mitsuo

    Macromolecules (Washington, DC, United States) (2010), 43 (13), 5595-5601CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)

    With judiciously selected ligands (phosphines) and cocatalysts (amines), a series of highly active and functionality-tolerant pentamethylcyclopentadienyl (Cp*) ruthenium catalysts [Cp*Ru(Cl)L1L2; L1 and L2: ligands] have been developed for living radical homo- and copolymns. universally accessible to a variety of functional methacrylates in ethanol and related alc. and polar media. In particular, the ligand/cocatalyst combination of tri-m-tolylphosphine [P(mTol)3; mTol = m-MeC6H5] and a hydrophilic amine, 2-dimethylamino-1-ethanol [Me2N(CH2)2OH; 2-DMAE], led to a very active and robust catalyst that induced fast polymns. and fine mol.-wt. control (Mw/Mn < 1.2) in ethanol for not only homopolymns. but also random or block copolymns. with pendent-functional methacrylates carrying poly(ethylene glycol) (-PEG), dimethylamino [-N(CH3)2], and hydroxyl (-OH) groups. The accessible solvents included a wide variety of alcs. (methanol, ethanol, etc.), environmentally benign and readily recoverable, in which high reaction rate and soln. homogeneity readily were attained for the polar monomers. 31P NMR anal. on the catalyst/cocatalyst systems revealed that a part of the starting coordinatively satd. 18e complex Cp*Ru(Cl)[P(mTol)3]2 is dynamically transformed in situ into an amine-coordinated analog Cp*Ru(Cl)[P(mTol)3](2-DMAE), and this dynamic ligand-cocatalyst exchange may in turn generate a transient unsatd. 16e form Cp*Ru(Cl)[P(mTol)3] that may be the "real" active catalyst. The products thus included homopolymers, AB- and ABC-block copolymers, and random/statistical copolymers; the last could be extended to as many as six functional comonomers, while retaining compositional uniformity and narrow mol. wt. distributions independent of monomer conversion.

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31. 31

    Fukuzaki, Y.; Tomita, Y.; Terashima, T.; Ouchi, M.; Sawamoto, M. Bisphosphine Monooxide-Ligated Ruthenium Catalysts: Active, Versatile, Removable, and Cocatalyst-Free in Living Radical Polymerization. Macromolecules 2010, 43, 5989– 5955,  DOI: 10.1021/ma100871n

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    31

    Bisphosphine Monoxide-Ligated Ruthenium Catalysts: Active, Versatile, Removable, and Cocatalyst-Free in Living Radical Polymerization

    Fukuzaki, Yusuke; Tomita, Yusuke; Terashima, Takaya; Ouchi, Makoto; Sawamoto, Mitsuo

    Macromolecules (Washington, DC, United States) (2010), 43 (14), 5989-5995CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)

    As potentially bidentate ligands, bisphosphine monoxides [BPMOs; Ph2P(O)(CH2)nPPh2; n = 1, 2; Ph = C6H5] were found to be effective for pentamethylcyclopentadiene ruthenium chloride catalysts [Cp*RuIICl(BPMO)m; m = 1,2] in living radical polymn.: active, versatile, cocatalyst-free, and removable. The complexes catalyzed living radical polymns. of a variety of monomers and their functionalized derivs.: Me acrylate, Me methacrylate (MMA), styrene, 2-hydroxyethyl methacrylate, and poly(ethylene glycol) methacrylate. The controllability and activity were high enough even with a small amt. of catalyst ([Ru]0/[initiator]0 = 1/200; 50 ppm for monomer), to give high mol. wt. PMMA with narrow MWD (Mn = 103 000: Mw/Mn = 1.19) and block copolymers. Such an activity and a wide applicability in terms of monomers have been found for few Ru catalysts thus far. Importantly, they did not necessarily need a cocatalyst (aluminum alkoxide, amine, etc.) for their catalysis, in contrast to most of the other ruthenium catalysts that are effective only with a cocatalyst. The cocatalyst-free catalysis is concluded to be derived from the phosphine oxide moiety in BPMO, whose hemilabile coordination promotes the deactivation process [∼∼∼C· (growth active) → ---C-Cl (dormant)] and, in turn, accelerates the whole catalytic cycle (radical ↔ dormant; RuII ↔ RuIII). Furthermore, the high polarity of BPMO ligands effectively helped near perfect removal of the catalyst residue (>99.7% for PMMA) just by single repptn. into methanol.

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32. 32

    Morimoto, N.; Wakamura, M.; Muramatsu, K.; Toita, S.; Nakayama, M.; Shoji, W.; Suzuki, M.; Winnik, F. M. Membrane Translocation and Organelle-Selective Delivery Steered by Polymeric Zwitterionic Nanospheres. Biomacromolecules 2016, 17, 1523– 1535,  DOI: 10.1021/acs.biomac.6b00172

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    32

    Membrane Translocation and Organelle-Selective Delivery Steered by Polymeric Zwitterionic Nanospheres

    Morimoto, Nobuyuki; Wakamura, Masaru; Muramatsu, Kanna; Toita, Sayaka; Nakayama, Masafumi; Shoji, Wataru; Suzuki, Makoto; Winnik, Francoise M.

    Biomacromolecules (2016), 17 (4), 1523-1535CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)

    The majority of nanoparticles designed for cellular delivery of drugs and imaging agents enter the cell via endocytotic pathways leading to their entrapment in endosomes that present a robust barrier to further trafficking of the nanoparticles within the cells. A few materials, such as the cell penetrating peptides (CPPs), are known to enter cells not only via endocytosis, but also via translocation through the cell membrane into the cytoplasm, successfully bypassing the endosomes. We report here that random copolymers of 3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate and poly(ethylene glycol) methacrylate, p(DMAPS-ran-PEGMA), are internalized in cells primarily via translocation through the cell membrane rather than endocytosis. The properties of the polymers and their modes of uptake were investigated systematically by dynamic light scattering, confocal fluorescence microscopy, and flow cytometry. Using specific inhibitors of the cellular uptake machinery in a human cervical carcinoma cell line (HeLa), we show that these nontoxic synthetic polyzwitterions exist in cell media as self-assembled nanospheres that unravel as they adsorb on the plasma membrane and translocate through it. Conjugates of p(DMAPS-ran-PEGMA) with rhodamine B were delivered selectively to the mitochondria, whereas doxorubicin (Dox)-p(DMAPS-ran-PEGMA) conjugates were accumulated in both the nucleus and the mitochondria, effectively inducing apoptosis in HeLa cells. These findings suggest that the noncytotoxic and readily synthesized p(DMAPS-ran-PEGMA) can find applications as bioimaging tools and drug nanocarriers.

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33. 33

    Hinton, T. M.; Challagulla, A.; Stewart, C. R.; Guerrero-Sanchez, C.; Grusche, F. A.; Shi, S.; Bean, A. G.; Monaghan, P.; Gunatillake, P. A.; Thang, S. H.; Tizard, M. L. Inhibition of Influenza Virus In Vivo by siRNA Delivered Using ABA Triblock Copolymer Synthesized by Reversible Addition-Fragmentation Chain-Transfer Polymerization. Nanomedicine 2014, 9, 1141– 1154,  DOI: 10.2217/nnm.13.119

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    33

    Inhibition of influenza virus in vivo by siRNA delivered using ABA triblock copolymer synthesized by reversible addition-fragmentation chain-transfer polymerization

    Hinton, Tracey M.; Challagulla, Arjun; Stewart, Cameron R.; Guerrero-Sanchez, Carlos; Grusche, Felix A.; Shi, Shuning; Bean, Andrew G.; Monaghan, Paul; Gunatillake, Pathiraja A.; Thang, San H.; Tizard, Mark L.

    Nanomedicine (London, United Kingdom) (2014), 9 (8), 1141-1154CODEN: NLUKAC; ISSN:1743-5889. (Future Medicine Ltd.)

    Aim: Influenza virus remains a major threat, with outbreaks continuing to occur. Few treatment options are available and drug resistance can emerge rapidly. New drugs that can quickly be adapted to virus mutations are needed. Several highly effective siRNAs targeting influenza that inhibit virus replication are known; however, effective delivery of these siRNAs remains a challenge. The aim of this study was to demonstrate the safety and efficacy of ABA triblock copolymer-delivered siRNA to inhibit influenza virus replication in vivo. Materials & methods: We report on the delivery of a siRNA targeting the influenza virus in chicken embryos using an ABA triblock copolymer prepd. by reversible addn.-fragmentation chain-transfer polymn., contg. a central cationic block and two outer hydrophilic polyethylene glycol blocks. Results: A significant redn. of virus titer was obsd. with the polymer/anti-influenza siRNA complexes, whereas the control with polymer/control siRNA complexes showed no effect. Conclusion: These data suggest that a reversible addn.-fragmentation chain transfer-based siRNA delivery platform may be suitable for combating infectious diseases in vivo.Original submitted 21 Dec. 2012; Revised submitted 10 May 2013.

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34. 34

    Mann, S. K.; Dufour, A.; Glass, J. J.; Rose, R. D.; Kent, S. J.; Such, G. K.; Johnston, P. R. Tuning the Properties of pH Responsive Nanoparticles to Control Cellular Interactions In Vitro and Ex Vivo. Polym. Chem. 2016, 7, 6015– 6024,  DOI: 10.1039/C6PY01332E

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    34

    Tuning the properties of pH responsive nanoparticles to control cellular interactions in vitro and ex vivo

    Mann, S. K.; Dufour, A.; Glass, J. J.; De Rose, R.; Kent, S. J.; Such, G. K.; Johnston, A. P. R.

    Polymer Chemistry (2016), 7 (38), 6015-6024CODEN: PCOHC2; ISSN:1759-9962. (Royal Society of Chemistry)

    Engineering the properties of nanoparticles (NPs) to limit non-specific cellular interactions is crit. for developing effective drug delivery systems. In this study we investigate the differences in non-specific cell assocn. between polymer NPs prepd. with linear polyethylene glycol (PEG) and brush PEG both in vitro and ex vivo. Most studies to investigate the non-fouling properties of NPs have been performed using cell-line based assays. However, in this study we demonstrate a whole blood assay using fresh human blood. It is likely this assay reflects more accurately the fate of NPs when injected into human blood in vivo. Non-linear PEG analogs such as poly(poly(ethylene glycol)methacrylate) (PEGMA) are attractive alternatives to linear PEG as hydrophilic coatings for NP drug delivery systems due to their simple and versatile synthesis. We prepd. NPs composed of a poly(2-diethylamino)ethyl methacrylate (PDEAEMA) core and a diblock copolymer of PDEAEMA and either linear PEG or brush PEGMA. These NPs depend on low-fouling properties of the hydrophillic PEG coating to avoid uptake by the mononuclear phagocyte system (MPS). In vitro cell assocn. assays showed brush PEGMA NPs exhibited lower assocn. with 3T3 fibroblast and C1R lymphoblast cells compared to linear PEG NPs. In an ex vivo whole blood assay, brush PEGMA nanoparticles showed similar low assocn. with monocytes and granulocytes as linear PEG NPs with a similar length PEG component. Higher assocn. with blood cells was obsd. for NPs contg. a lower mol. wt. PEGMA component, despite having the same mol. wt. as the linear PEG NPs (2 kDa). The results demonstrate that trends obsd. in cell-lines are not always consistent with assays in more complex systems such as blood. Based on these results the reported PEGMA NPs are attractive alternatives to our previously reported linear PEG NPs.

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35. 35

    Sun, H.; Cui, J.; Ju, Y.; Chen, X.; Wong, E. H. H.; Tran, J.; Qiao, G. G.; Caruso, F. Tuning the Properties of Polymer Capsules for Cellular Interactions. Bioconjugate Chem. 2017, 28, 1859– 1866,  DOI: 10.1021/acs.bioconjchem.7b00168

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    35

    Tuning the Properties of Polymer Capsules for Cellular Interactions

    Sun, Huanli; Cui, Jiwei; Ju, Yi; Chen, Xi; Wong, Edgar H. H.; Tran, Jenny; Qiao, Greg G.; Caruso, Frank

    Bioconjugate Chemistry (2017), 28 (7), 1859-1866CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)

    Particle-cell interactions are governed by, among other factors, the compn. and surface properties of the particles. Herein, we report the prepn. of various polymer capsules with different compns. and properties via atom transfer radical polymn. mediated continuous assembly of polymers (CAPATRP), where the cellular interactions of these capsules, particularly fouling and specific targeting, are examd. by flow cytometry and deconvolution microscopy. Acrylated eight-arm poly(ethylene glycol) (8-PEG) and poly(N-(2-hydroxypropyl)-methacrylamide) (PHPMA) as well as methacrylated hyaluronic acid (HA), poly(glutamic acid) (PGA), and poly(methacrylic acid) (PMA) are used as macro-cross-linkers to obtain a range of polymer capsules with different compns. (PEG, PHPMA, HA, PGA, and PMA). Capsules composed of low-fouling polymers, PEG and PHPMA, show negligible assocn. with macrophage Raw 264.7, monocyte THP-1, and HeLa cells. HA capsules, although moderately low-fouling (<22%) to HeLa, BT474, Raw 264.7, and THP-1 cells, exhibit high targeting specificity to CD44-over-expressing MDA-MB-231 cells. In contrast, PGA and PMA capsules show high cellular assocn. toward phagocytic Raw 264.7 and THP-1 cells. These findings demonstrate the capability of the CAPATRP technique in prepg. polymer capsules with specific cellular interactions.

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36. 36

    Takahashi, D.; Koda, Y.; Sasaki, Y.; Akiyoshi, K. Design and Synthesis of PEGylated Amphiphilic Block Oligomers as Membrane Anchors for Stable Binding to Lipid Bilayer Membranes. Polym. J. 2018, 50, 787– 797,  DOI: 10.1038/s41428-018-0055-5

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    36

    Design and synthesis of PEGylated amphiphilic block oligomers as membrane anchors for stable binding to lipid bilayer membranes

    Takahashi, Daiki; Koda, Yuta; Sasaki, Yoshihiro; Akiyoshi, Kazunari

    Polymer Journal (Tokyo, Japan) (2018), 50 (8), 787-797CODEN: POLJB8; ISSN:0032-3896. (Nature Research)

    Cell surface engineering is a potentially powerful method for manipulating living cells by decorating the cell membrane with specific mols. Possible applications include cell therapy, drug delivery systems, bio-imaging, and tissue engineering. The stable binding of synthetic mols. to serve as artificial membrane protein anchors is a promising approach for appending functional mols. to the cell surface. However, such synthetic mols. have previously shown limitations, including cytotoxicity and low cell surface affinity. We synthesized amphiphilic block oligomers, using ruthenium-catalyzed living radical polymn., as novel membrane anchors for stable binding to lipid bilayer membranes. AB and ABA-type amphiphilic block oligomers were synthesized with poly(ethylene glycol) methacrylate (PEGMA) and varying Bu methacrylate (BMA) contents (PEGMA/BMA ratios of 25/5-25/50). These PEGylated oligomers showed high binding efficiencies (up to 92%) for liposomes, which served as model cell membranes, and low cytotoxicity in K562 cells. Both the BMA content and the block segment sequence in the copolymers strongly affected their binding efficiencies. Oligomers with an ABA-type block structure were much more effective than AB-type block oligomers, random oligomers, or PEGMA homo-oligomers for stable membrane binding. Thus, precise control of the primary structures of the amphiphilic oligomers enabled tuning of their binding efficiencies. These amphiphilic block oligomers hold promise as novel membrane anchors in many biomedical applications.

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37. 37

    Matyjaszewski, K.; Tsarevsky, N. V. Macromolecular Engineering by Atom Transfer Radical Polymerization. J. Am. Chem. Soc. 2014, 136, 6513– 6533,  DOI: 10.1021/ja408069v

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    37

    Macromolecular Engineering by Atom Transfer Radical Polymerization

    Matyjaszewski, Krzysztof; Tsarevsky, Nicolay V.

    Journal of the American Chemical Society (2014), 136 (18), 6513-6533CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    A review. This Perspective presents recent advances in macromol. engineering enabled by ATRP. They include the fundamental mechanistic and synthetic features of ATRP with emphasis on various catalytic/initiation systems that use parts-per-million concns. of Cu catalysts and can be run in environmentally friendly media, e.g., water. The roles of the major components of ATRP-monomers, initiators, catalysts, and various additives-are explained, and their reactivity and structure are correlated. The effects of media and external stimuli on polymn. rates and control are presented. Some examples of precisely controlled elements of macromol. architecture, such as chain uniformity, compn., topol., and functionality, are discussed. Syntheses of polymers with complex architecture, various hybrids, and bioconjugates are illustrated. Examples of current and forthcoming applications of ATRP are covered. Future challenges and perspectives for macromol. engineering by ATRP are discussed.

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38. 38

    Anastasaki, A.; Nikolaou, V.; Nurumbetov, G.; Wilson, P.; Kempe, K.; Quinn, J. F.; Davis, T. P.; Whittaker, M. R.; Haddleton, D. M. Cu(0)-Mediated Living Radical Polymerization: A Versatile Tool for Materials Synthesis. Chem. Rev. 2016, 116, 835– 877,  DOI: 10.1021/acs.chemrev.5b00191

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    38

    Cu(0)-Mediated Living Radical Polymerization: A Versatile Tool for Materials Synthesis

    Anastasaki, Athina; Nikolaou, Vasiliki; Nurumbetov, Gabit; Wilson, Paul; Kempe, Kristian; Quinn, John F.; Davis, Thomas P.; Whittaker, Michael R.; Haddleton, David M.

    Chemical Reviews (Washington, DC, United States) (2016), 116 (3), 835-877CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)

    A review. The scope of this review is to highlight Cu(0)-mediated living radical polymn. (or single electron transfer living radical polymn. (SET-LRP)) as an efficient polymn. mothodol. providing access to a large variety of materials and complex macromol. architectures. The review will focus in the developments on this area since 2009, when a previous review was published by Percec and Rosen, although a brief overview of SET-LRP is also included. Special emphasis will be given to the applications of SET-LRP for the prepn. of novel materials in both biol. and technol. realms. Historical details regarding the genesis of SET-LRP and the evolution from single electron degenerative transfer living radical polymn. (SET-DTLRP) were addressed in detail in the aforementioned review and will not be revisited herein. The mechanistic debate will also be critically discussed; however, it is not the main focus of this current contribution.

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39. 39

    Zhang, Q.; Wilson, P.; Li, Z.; McHale, R.; Godfrey, J.; Anastasaki, A.; Waldron, C.; Haddleton, D. M. Aqueous Copper-Mediated Living Polymerization: Exploiting Rapid Disproportionation of CuBr with Me₆TREN. J. Am. Chem. Soc. 2013, 135, 7355– 7363,  DOI: 10.1021/ja4026402

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    39

    Aqueous Copper-Mediated Living Polymerization: Exploiting Rapid Disproportionation of CuBr with Me6TREN

    Zhang, Qiang; Wilson, Paul; Li, Zaidong; McHale, Ronan; Godfrey, Jamie; Anastasaki, Athina; Waldron, Christopher; Haddleton, David M.

    Journal of the American Chemical Society (2013), 135 (19), 7355-7363CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    A new approach to perform single-electron transfer living radical polymn. (SET-LRP) in water is described. The key step in this process is to allow full disproportionation of CuBr/Me6TREN (TREN = tris(dimethylamino)ethyl amine) to Cu(0) powder and CuBr2 in water prior to addn. of both monomer and initiator. This provides an extremely powerful tool for the synthesis of functional water-sol. polymers with controlled chain length and narrow mol. wt. distributions (polydispersity index approx. 1.10), including poly(N-isopropylacrylamide), N,N-dimethylacrylamide, poly(ethylene glycol) acrylate, 2-hydroxyethyl acrylate (HEA), and an acrylamido glyco monomer. The polymns. are performed at or below ambient temp. with quant. conversions attained in minutes. Polymers have high chain end fidelity capable of undergoing chain extensions to full conversion or multiblock copolymn. via iterative monomer addn. after full conversion. Activator generated by electron transfer atom transfer radical polymn. of N-isopropylacrylamide in water was also conducted as a comparison with the SET-LRP system. This shows that the addn. sequence of L-ascorbic acid is crucial in detg. the onset of disproportionation, or otherwise. Finally, this robust technique was applied to polymns. under biol. relevant conditions (PBS buffer) and a complex ethanol/water mixt. (tequila).

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40. 40

    Alsubaie, F.; Anastasaki, A.; Nikolaou, V.; Simula, A.; Nurumbetov, G.; Wilson, P.; Kempe, K.; Haddleton, D. M. Investigating the Mechanism of Copper(0)-Mediated Living Radical Polymerization in Organic Media. Macromolecules 2015, 48, 5517– 5525,  DOI: 10.1021/acs.macromol.5b01197

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    40

    Investigating the Mechanism of Copper(0)-Mediated Living Radical Polymerization in Organic Media

    Alsubaie, Fehaid; Anastasaki, Athina; Nikolaou, Vasiliki; Simula, Alexandre; Nurumbetov, Gabit; Wilson, Paul; Kempe, Kristian; Haddleton, David M.

    Macromolecules (Washington, DC, United States) (2015), 48 (16), 5517-5525CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)

    Single electron transfer living radical polymn. (SET-LRP) is a versatile polymn. tool that allows for the synthesis of functional materials for a range of potential applications. An interesting scientific debate has dominated the literature during the past few years regarding the mechanism of Cu(0)-mediated polymns. in both aq. and org. media. This article is the first part of a mechanistic study regarding the role of Cu(0) and CuBr in these systems with the aim of offering some increased level of understanding of the mechanism to aid application. In this current contribution, disproportionation and comproportionation studies reveal significant variations in the thermodn. and kinetic equil. depending on the solvent compn., the nature of the monomer and the ligand concn. Interestingly, the sequence of reagent addn. significantly affects the disproportionation equil., which is attributed to competitive complexation reactions between monomer, solvent, ligand, and copper species. The Cu(0) generated via the in situ disproportionation of [Cu(Me6TREN)]Br in DMSO prior to addn. of monomer and initiator were demonstrated to contribute in different extents over the rate and control of the polymn., depending on the equiv. of ligand employed. It was found that an increase in the concn. of the Cu(0) particles result in slower polymn. rates while when conditions that stabilize CuBr were employed, faster polymn. rates were obsd. On the contrary, 5 cm of copper wire showed faster polymn. rates when compared with 9.4 mM of CuBr, highlighting that copper wire is essential for the efficient polymn. of acrylates in org. solvents.

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41. 41

    Alsubaie, F.; Anastasaki, A.; Nikolaou, V.; Simula, A.; Nurumbetov, G.; Wilson, P.; Kempe, K.; Haddleton, D. M. Investigating the Mechanism of Copper(0)-Mediated Living Radical Polymerization in Aqueous Media. Macromolecules 2015, 48, 6421– 6432,  DOI: 10.1021/acs.macromol.5b01208

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    41

    Investigating the Mechanism of Copper(0)-Mediated Living Radical Polymerization in Aqueous Media

    Alsubaie, Fehaid; Anastasaki, Athina; Nikolaou, Vasiliki; Simula, Alexandre; Nurumbetov, Gabit; Wilson, Paul; Kempe, Kristian; Haddleton, David M.

    Macromolecules (Washington, DC, United States) (2015), 48 (18), 6421-6432CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)

    This article is the second part of a mechanistic study regarding the role of Cu(0) and CuBr during the Cu(0)-mediated polymn. in org. and aq. media with the aim of offering a better understanding of the mechanism. In this contribution, we focus on disproportionation and comproportionation studies in aq. and org./aq. media in the presence of either Cu(0) generated in situ and Cu(0) wire. The solvent compn., the nature of the monomer and the ligand concn. dramatically affect the thermodn. and kinetic equil. while changing the sequence of the reagent addn. caused significant variations not only on the disproportionation equil. but also on the dispersities of the products obtained. This was attributed to different complexation reactions between the monomer, the solvent, the ligand, and the copper species. Reagent feeding expts. with low concns. of CuBr were also conducted in an attempt to mimic the role of Cu(0) as a potential supplemental activator, further assessing the contributions of Cu(0) and CuBr on the polymn. rate and control over the mol. wt. distributions in the presence of either disproportionating (Me6TREN) and nondisproportionating (TPMA) ligands. Crucially, the exploitation of stoichiometric amts. of Cu(0) and CuBr relative to CuBr2 allowed for a direct comparison between the SET-LRP and atom transfer living radical polymn. (ATRP) protocols, revealing very different contributions of the two catalysts depending on the conditions employed.

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42. 42

    Thomson, D. A. C.; Tee, E. H. L.; Tran, N. T. D.; Monteiro, M. J.; Cooper, M. A. Oligonucleotide and Polymer Functionalized Nanoparticles for Amplification-Free Detection of DNA. Biomacromolecules 2012, 13, 1981– 1989,  DOI: 10.1021/bm300717f

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    42

    Oligonucleotide and polymer functionalized nanoparticles for amplification-free detection of DNA

    Thomson, David A. C.; Tee, Ernest H. L.; Tran, Nguyen T. D.; Monteiro, Michael J.; Cooper, Matthew A.

    Biomacromolecules (2012), 13 (6), 1981-1989CODEN: BOMAF6; ISSN:1525-7797. (American Chemical Society)

    Sensitive and quant. nucleic acid testing from complex biol. samples is now an important component of clin. diagnostics. Whereas nucleic acid amplification represents the gold std., its utility in resource-limited and point-of-care settings can be problematic due to assay interferants, assay time, engineering constraints, and costs assocd. with both wetware and hardware. In contrast, amplification-free nucleic acid testing can circumvent these limitations by enabling direct target hybridization within complex sample matrixes. In this work, the authors grew random copolymer brushes from the surface of silica-coated magnetic nanoparticles using azide-modified and hydroxyl oligo ethylene glycol methacrylate (OEGMA) monomers. The azide-functionalized polymer brush was first conjugated, via copper-catalyzed azide/alkyne cycloaddn. (CuAAC), with herpes simplex virus (HSV)-specific oligonucleotides and then with alkyne-substituted polyethylene glycol to eliminate all residual azide groups. This methodol. enabled control over brush thickness and probe d. and enabled multiple consecutive coupling reactions on the particle grafted brush. Brush- and probe-modified particles were then combined in a 20 min hybridization with fluorescent polystyrene nanoparticles modified with HSV-specific reporter probes. Following magnetic capture and washing, the particles were analyzed with an aggregate fluorescence measurement, which yielded a limit of detection of 6 pM in buffer and 60 pM in 50% fetal bovine serum. Adoption of brush- and probe-modified particles into a particle counting assay will result in the development of diagnostic assays with significant improvements in sensitivity.

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43. 43

    Pramanik, P.; Halder, D.; Jana, S. S.; Ghosh, S. pH-Triggered Sustained Drug Delivery from a Polymer Micelle Having the β-Thiopropionate Linkage. Macromol. Rapid Commun. 2016, 37, 1499– 1506,  DOI: 10.1002/marc.201600260

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    Ouchi, M.; Yoda, H.; Terashima, T.; Sawamoto, M. Aqueous Metal-Catalyzed Living Radical Polymerization: Highly Active Water-Assisted Catalysis. Polym. J. 2012, 44, 51– 58,  DOI: 10.1038/pj.2011.59

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    Aqueous metal-catalyzed living radical polymerization: highly active water-assisted catalysis

    Ouchi, Makoto; Yoda, Hiroaki; Terashima, Takaya; Sawamoto, Mitsuo

    Polymer Journal (Tokyo, Japan) (2012), 44 (1), 51-58CODEN: POLJB8; ISSN:0032-3896. (NPG Nature Asia-Pacific)

    Catalytic aq. living radical polymn. was achieved through a ligand design for a ruthenium-based catalyst. A phenolic phosphine ligand [PPh2(pPhOH)] was combined with a pentamethylcyclopentadienyl (Cp*)-based tetrameric ruthenium precursor, and the resulting complex showed a high catalytic activity for aq. living radical polymns. of hydrophilic methacrylates (for example, poly(ethylene glycol) methacrylate and 2-hydroxyethyl methacrylate) in conjunction with a chlorine initiator [H-(MMA)2-Cl]. The catalytic system allowed very fast living polymns., block copolymns. and syntheses of high-mol.-wt. polymers (DPn∼1000) with narrow-mol.-wt. distributions. Importantly, the activity was high enough to control the polymn. using a catalytic amt. of the complex, even though the polymns. were performed at low temp. (40 °C). Such advanced catalysis was achieved by not only simple hydrophilicity of the ligand but also by a water-assisted dynamic transformation from the original coordinatively satd. form [Cp*RuCl(PR3)2; 18e; PR3=phosphine] into an unsatd. and active form [Cp*RuCl(PR3); 16e]. Water mol.(s) may also coordinate for further stabilization as demonstrated by 31P NMR analyses.

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45. 45

    Terashima, T.; Ouchi, M.; Ando, T.; Kamigaito, M.; Sawamoto, M. Amphiphilic, Thermosensitive Ruthenium(II)-Bearing Star Polymer Catalysts: One-Pot Synthesis of PEG Armed Star Polymers with Ruthenium(II)-Enclosed Microgel Cores via Metal-Catalyzed Living Radical Polymerization. Macromolecules 2007, 40, 3581– 3588,  DOI: 10.1021/ma062446r

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    45

    Amphiphilic, Thermosensitive Ruthenium(II)-Bearing Star Polymer Catalysts: One-Pot Synthesis of PEG Armed Star Polymers with Ruthenium(II)-Enclosed Microgel Cores via Metal-Catalyzed Living Radical Polymerization

    Terashima, Takaya; Ouchi, Makoto; Ando, Tsuyoshi; Kamigaito, Masami; Sawamoto, Mitsuo

    Macromolecules (Washington, DC, United States) (2007), 40 (10), 3581-3588CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)

    Amphiphilic and thermosensitive star polymers with Ru(II) complex-encapsulating microgel cores were directly synthesized in high yield via RuCl2(PPh3)3-catalyzed living radical polymn. For the solvo- and thermal responsiveness, the arms stem from a block copolymer of poly(ethylene glycol) Me ether methacrylate (PEGMA) with a small amt. of Me methacrylate. For the metal encapsulation into the core, a phosphine-ligand monomer [CH2:CH(C6H4)PPh2] was "copolymd." with a divinyl compd. (linking agent); upon block polymer formation, in situ addn. of these two components induced the linking reaction of the arm chains and, subsequently, the formation of Ru(II)-bearing microgels (cores) via ligand exchange between the triphenylphoshines in the original catalyst and the pendent phosphines in the core network. Thus, the hydrophobic catalyst [RuCl2(PPh3)3] for polymn. was in situ transformed into an amphiphilic core-bound catalyst. The star polymers with different Ru(II) contents were prepd. by changing the ratio of the ligand monomer to the living end (or the initiator). Even after isolation and exhaustive purifn., the polymers colored dark red-brown and accordingly exhibited UV-vis absorptions similar to those of RuCl2(PPh3)3, confirming the encapsulation of Ru(II) complexes into the core, from which the Ru(II) content was estd. in the range of 24-39 μmol/g of polymer, or 35-60 mol% of the originally added catalyst. The products were further characterized by SEC-MALLS in DMF: f(arm no.) = 19-53 per polymer; Mw=7.7×105 to 2.2×106; and Rz (radius of gyration)=15-22 nm. The PEG-armed star polymers were also amphiphilic (sol. in both alcs. and water) and thermosensitive (UCST near 30° in 2-propanol).

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46. 46

    Kawaguchi, T.; Kojima, Y.; Osa, M.; Yoshizaki, T. Cloud Points in Aqueous Poly(N-isopropylacrylamide) Solutions. Polym. J. 2008, 40, 455– 459,  DOI: 10.1295/polymj.PJ2007227

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    46

    Cloud points in aqueous poly(N-isopropylacrylamide) solutions

    Kawaguchi, Tomoaki; Kojima, Yosuke; Osa, Masashi; Yoshizaki, Takenao

    Polymer Journal (Tokyo, Japan) (2008), 40 (5), 455-459CODEN: POLJB8; ISSN:0032-3896. (Society of Polymer Science, Japan)

    The cloud point was detd. for aq. solns. of four kinds of poly(N-isopropylacrylamide) samples synthesized by radical polymn. in methanol, tert-butanol, benzene, and 1,4-dioxane by the use of azobis(isobutyronitrile) initiator, for samples of wt. fraction 0.5-10%. The cloud point so detd. for samples synthesized in benzene and 1,4-dioxane was definitely lower than that for samples synthesized in methanol and tert-butanol, although all the samples have almost the same stereochem. compn. and the same end group. The obsd. deviation may be regarded as arising from the difference in the primary structure between the samples.

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47. 47

    Cao, J.; Wang, K.; Yang, H.; Chen, F.; Zhang, Q.; Fu, Q. Shear-Induced Clay Dispersion in HDPE/PEgMA/Organoclay Composites as Studied via Real-Time Rheological Method. J. Polym. Sci., Part B: Polym. Phys. 2010, 48, 302– 312,  DOI: 10.1002/polb.21881

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    47

    Shear-induced clay dispersion in HDPE/PEgMA/organoclay composites as studied via real-time rheological method

    Cao, Jing; Wang, Ke; Yang, Hong; Chen, Feng; Zhang, Qin; Fu, Qiang

    Journal of Polymer Science, Part B: Polymer Physics (2010), 48 (3), 302-312CODEN: JPBPEM; ISSN:0887-6266. (John Wiley & Sons, Inc.)

    In current study, a real-time rheol. method was used to investigate the intercalation and exfoliation process of clay in high-d. polyethylene/organoclay (HDPE/OMMT) nanocomposites using maleic anhydride grafted polyethylene (PEgMA) as compatibilizer. To do this, a steady shear was applied to the original nonintercalated or slightly intercalated composites prepd. via simple mixing. The moduli of the composites were recorded as a function of time. The effect of matrix mol. wt. and the content of compatibilizer on the modulus were studied. The role of the compatibilizer is to enhance the interaction between OMMT and polymer matrix, which facilitates the dispersion, intercalation, and exfoliation of OMMT. The matrix mol. wt. dets. the melt viscosity and affects the shear stress applied to OMMT platelets. Based on the exptl. results, different exfoliation processes of OMMT in composites with different matrix mol. wt. were demonstrated. The slippage of OMMT layers is suggested in low-mol. wt. matrix, whereas a gradual intercalation process under shear is suggested in high-mol. wt. matrix. Current study demonstrates that real-time rheol. measurement is an effective way to investigate the dispersion, intercalation, and exfoliation of OMMT as well as the structural change of the matrix. Moreover, it also provides a deep understanding for the role of polymer matrix and compatibilizer in the clay intercalation process. 2009 Wiley Periodicals, Inc., J Polym Sci Part B: Polym Phys 48: 302-312, 2010.

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48. 48

    Kai, D.; Low, Z. W.; Liow, S. S.; Karim, A. A.; Ye, H.; Jin, G.; Li, K.; Loh, X. J. Development of Lignin Supramolecular Hydrogels with Mechanically Responsive and Self-Healing Properties. ACS Sustainable Chem. Eng. 2015, 3, 2160– 2169,  DOI: 10.1021/acssuschemeng.5b00405

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    48

    Development of Lignin Supramolecular Hydrogels with Mechanically Responsive and Self-Healing Properties

    Kai, Dan; Low, Zhi Wei; Liow, Sing Shy; Abdul Karim, Anis; Ye, Hongye; Jin, Guorui; Li, Kai; Loh, Xian Jun

    ACS Sustainable Chemistry & Engineering (2015), 3 (9), 2160-2169CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)

    The development of functional polymers from renewable lignin is attractive due to the depletion of fossil fuel and increasing environmental usage. A series of poly(ethylene glycol) Me ether methacrylate (PEGMA)-grafted lignin hyperbranched copolymers were prepd. by atom transfer radical polymn. (ATRP). The chem. structures, mol. characteristic and thermal properties of these copolymers were evaluated and such copolymers were prepd. in a range of mol. wts. from 38.7 to 65.0 kDa by adjusting the PEGMA-to-lignin wt. ratio. As a result from their hyperbranch architecture, their aq. solns. were found to form supramol. hydrogels with a very low crit. gelation concn. of 1 wt. % copolymers, in the presence of α-cyclodextrin (α-CD). The rheol. properties of the supramol. assemblies were investigated and these hydrogel systems showed tunable mech. response and excellent self-healing capability. Combined with good biocompatibility, these new types of green supramol. hydrogels based on lignin-PEGMA/cyclodextrin inclusion are potentially useful as a smart biomaterial for biomedical application.

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49. 49

    Ward, M. A.; Georgiou, T. K. Thermoresponsive Terpolymers Based on Methacrylate Monomers: Effect of Architecture and Composition. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 775– 783,  DOI: 10.1002/pola.23825

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    49

    Thermoresponsive terpolymers based on methacrylate monomers: Effect of architecture and composition

    Ward, Mark A.; Georgiou, Theoni K.

    Journal of Polymer Science, Part A: Polymer Chemistry (2010), 48 (4), 775-783CODEN: JPACEC; ISSN:0887-624X. (John Wiley & Sons, Inc.)

    A series of amphiphilic thermoresponsive copolymers was synthesized by group transfer polymn. Seven copolymers were prepd. based on the nonionic hydrophobic Bu methacrylate (BuMA), the ionizable hydrophilic and thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the nonionic hydrophilic poly(ethylene glycol)methyl methacrylate (PEGMA). In particular, one diblock copolymer and six tricomponent copolymers of different architectures and compns., one random and five triblock copolymers, were synthesized. The polymers and their precursors were characterized in terms of their mol. wt. and compn. using gel permeation chromatog. and proton NMR spectroscopy, resp. Aq. solns. of the polymers were studied by turbidimetry, hydrogen ion titrn., and light scattering to det. their cloud points, pKas, and hydrodynamic diams. and investigate the effect of the polymers' compn. and architecture. The thermoresponsive behavior of the copolymers was also studied. By increasing the temp., all polymer solns. became more viscous, but only one polymer, the one with the highest content of the hydrophobic BuMA, formed a stable phys. gel. Interestingly, the thermoresponsive behavior of these triblock copolymers was affected not only by the terpolymers' compn. but also by the terpolymers' architecture. These findings can facilitate the design and engineering of injectable copolymers for tissue engineering that could enable the in situ formation of phys. gels at body temp.

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50. 50

    Iborra, A.; Díaz, G.; López, D.; Giussi, J. M.; Azzaroni, O. Copolymer Based on Lauryl Methacrylate and Poly(ethylene glycol) Methyl Ether Methacrylate as Amphiphilic Macrosurfactant: Synthesis, Characterization and Their Application as Dispersing Agent for Carbon Nanotubes. Eur. Polym. J. 2017, 87, 308– 317,  DOI: 10.1016/j.eurpolymj.2016.12.027

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    50

    Copolymer based on lauryl methacrylate and poly(ethylene glycol) methyl ether methacrylate as amphiphilic macrosurfactant: Synthesis, characterization and their application as dispersing agent for carbon nanotubes

    Iborra, Agustin; Diaz, Gisela; Lopez, Daniel; Giussi, Juan Martin; Azzaroni, Omar

    European Polymer Journal (2017), 87 (), 308-317CODEN: EUPJAG; ISSN:0014-3057. (Elsevier Ltd.)

    The use of amphiphilic macrosurfactants as emulsifying agents has shown to have higher efficiency than that of low mol. wt. surfactants. Compared to traditional surfactants, polymeric surfactants have lower crit. micelle concns. and lower diffusion coeffs. In this paper, we present a well defined copolymer based on lauryl methacrylate and poly(ethylene glycol) Me ether methacrylate, prepd. by soln. radical copolymn. The product was characterized by NMR and FTIR spectroscopies and the wt.-av. mol. wt. and polydispersity index were analyzed by SEC. The thermal transitions and decompn. temps. of the copolymers were detd. by DSC and TGA, resp. Due to the hydrophobic and hydrophilic nature of the monomer units, emulsification studies were performed. DLS expts. showed different sizes of the formed micelles depending on solvent polarity due to polymer-polymer or polymer-solvent interactions. Rheol. characterization was undertaken to study the viscoelastic properties of the dispersed systems. Finally, two types of expts. to evaluate the polymer abilities as surfactant were carried out. Firstly, the amphiphilic characteristics of this material allowed the incorporation of small amts. of an org. solvent in water forming only one phase, and the incorporation of small amts. of water in the org. solvent forming an emulsified phase. Then, the amphiphilic properties of this macrosurfactant were fully exploited to form highly stable dispersions of carbon nanotubes in water.

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51. 51

    Watanabe, H.; Matsumiya, Y.; Inoue, T. Dielectric and Viscoelastic Relaxation of Highly Entangled Star Polyisoprene: Quantitative Test of Tube Dilation Model. Macromolecules 2002, 35, 2339– 2357,  DOI: 10.1021/ma011782z

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    51

    Dielectric and Viscoelastic Relaxation of Highly Entangled Star Polyisoprene: Quantitative Test of Tube Dilation Model

    Watanabe, Hiroshi; Matsumiya, Yumi; Inoue, Tadashi

    Macromolecules (2002), 35 (6), 2339-2357CODEN: MAMOBX; ISSN:0024-9297. (American Chemical Society)

    For highly entangled cis-polyisoprene (PI) star polymers having more than 10 entanglements in each arm, dielec. and viscoelastic properties were examd. within a context of the generalized tube model incorporating the dynamic tube dilation (DTD) mechanism. The star PI had the type A dipoles parallel along the arm backbone, and the global motion results in the viscoelastic as well as dielec. relaxation. The DTD relationship between the dielec. and viscoelastic relaxation functions Φ(t) and μ(t), μ(t) equiv. [Φ(t)]2 (derived under an assumption of random displacement of the entanglement segment in the dilated tube edge), was not valid for the star PI. Furthermore, the DTD model (Milner-McLeish model) excellently described the viscoelastic data, but considerable differences were found for the dielec. data, even if an effect of the segment displacement in the tube edge was considered in the model. These results indicated a failure of the DTD mol. picture for a few entanglement segments near the branching point. Thus, these segments near the branching point appeared to fully relax via the constraint release (CR) mechanism before the expected tube dilation was completed. On the basis of this result, the DTD model was modified by explicitly incorporating this CR process (though in a crude way). This modification moderately improved the model prediction, suggesting a possible direction of further refinement of the model.

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