Tailored Design of Au Nanoparticle-siRNA Carriers Utilizing Reversible Addition−Fragmentation Chain Transfer Polymers∥
- Stacey Kirkland-York ,
- Yilin Zhang ,
- Adam E. Smith ,
- Adam W. York ,
- Faqing Huang , and
- Charles L. McCormick
Abstract

The facile synthesis of polymer-stabilized Au nanoparticles (AuNPs) capable of forming neutral, sterically stable complexes with small interfering RNA (siRNA) is reported. The amine-containing cationic block of poly(N-2-hydroxypropyl methacrylamide70-block-N-[3-(dimethylamino)propyl] methacrylamide24) [P(HPMA70-b-DMAPMA24)] was utilized to promote the in situ reduction of Au3+ to AuNPs and subsequently bind small interfering RNA, while the nonimmunogenic, hydrophilic block provided steric stabilization. The ratio of [DMAPMA]0/[Au3+]0 utilized in the reduction reaction was found to be critical to the production of polymer-stabilized AuNPs capable of complexing siRNA. Significant protection (∼100 times) against nucleases was demonstrated by enzymatic tests, while gene down-regulation experiments indicated successful delivery of siRNA to cancerous cells.
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- Pratyawadee Singhsa, Diana Diaz-Dussan, Hathaikarn Manuspiya, and Ravin Narain . Well-Defined Cationic N-[3-(Dimethylamino)propyl]methacrylamide Hydrochloride-Based (Co)polymers for siRNA Delivery. Biomacromolecules 2018, 19 (1) , 209-221. https://doi.org/10.1021/acs.biomac.7b01475
- Vivek Arjunan Vasantha, Chen Junhui, Tay Boon Ying, and Anbanandam Parthiban . Salt-Responsive Polysulfabetaines from Acrylate and Acrylamide Precursors: Robust Stabilization of Metal Nanoparticles in Hyposalinity and Hypersalinity. Langmuir 2015, 31 (40) , 11124-11134. https://doi.org/10.1021/acs.langmuir.5b01768
- Hongmei Li, Martina Miteva, Kellye C. Kirkbride, Ming J. Cheng, Christopher E. Nelson, Elaine M. Simpson, Mukesh K. Gupta, Craig L. Duvall, and Todd D. Giorgio . Dual MMP7-Proximity-Activated and Folate Receptor-Targeted Nanoparticles for siRNA Delivery. Biomacromolecules 2015, 16 (1) , 192-201. https://doi.org/10.1021/bm501394m
- Meihua Yu, Yuting Niu, Yannan Yang, Sandy Budi Hartono, Jie Yang, Xiaodan Huang, Peter Thorn, and Chengzhong Yu . An Approach to Prepare Polyethylenimine Functionalized Silica-Based Spheres with Small Size for siRNA Delivery. ACS Applied Materials & Interfaces 2014, 6 (18) , 15626-15631. https://doi.org/10.1021/am503060n
- Yaoying Wu, Miao Wang, Dustin Sprouse, Adam E. Smith, and Theresa M. Reineke . Glucose-Containing Diblock Polycations Exhibit Molecular Weight, Charge, and Cell-Type Dependence for pDNA Delivery. Biomacromolecules 2014, 15 (5) , 1716-1726. https://doi.org/10.1021/bm5001229
- Andrew C. Holley, Jacob G. Ray, Wenming Wan, Daniel A. Savin, and Charles L. McCormick . Endolytic, pH-Responsive HPMA-b-(l-Glu) Copolymers Synthesized via Sequential Aqueous RAFT and Ring-Opening Polymerizations. Biomacromolecules 2013, 14 (10) , 3793-3799. https://doi.org/10.1021/bm401205y
- Shann S. Yu, Cheryl M. Lau, Whitney J. Barham, Halina M. Onishko, Christopher E. Nelson, Hongmei Li, Chelsey A. Smith, Fiona E. Yull, Craig L. Duvall, and Todd D. Giorgio . Macrophage-Specific RNA Interference Targeting via “Click”, Mannosylated Polymeric Micelles. Molecular Pharmaceutics 2013, 10 (3) , 975-987. https://doi.org/10.1021/mp300434e
- Aneta J. Mieszawska, Willem J. M. Mulder, Zahi A. Fayad, and David P. Cormode . Multifunctional Gold Nanoparticles for Diagnosis and Therapy of Disease. Molecular Pharmaceutics 2013, 10 (3) , 831-847. https://doi.org/10.1021/mp3005885
- Jianliang Shen, Wei Zhang, Ruogu Qi, Zong-Wan Mao, Haifa Shen. Engineering functional inorganic–organic hybrid systems: advances in siRNA therapeutics. Chemical Society Reviews 2018, 47 (6) , 1969-1995. https://doi.org/10.1039/C7CS00479F
- Junbo Li, Sheng Zou, Jiayu Gao, Ju Liang, Huiyun Zhou, Lijuan Liang, Wenlan Wu. Block copolymer conjugated Au-coated Fe3O4 nanoparticles as vectors for enhancing colloidal stability and cellular uptake. Journal of Nanobiotechnology 2017, 15 (1) https://doi.org/10.1186/s12951-017-0290-5
- Aili Suo, Junmin Qian, Minghui Xu, Weijun Xu, Yaping Zhang, Yu Yao. Folate-decorated PEGylated triblock copolymer as a pH/reduction dual-responsive nanovehicle for targeted intracellular co-delivery of doxorubicin and Bcl-2 siRNA. Materials Science and Engineering: C 2017, 76 , 659-672. https://doi.org/10.1016/j.msec.2017.03.124
- Junbo Li, Wenlan Wu, Jiayu Gao, Ju Liang, Huiyun Zhou, Lijuan Liang. Constructing of DNA vectors with controlled nanosize and single dispersion by block copolymer coating gold nanoparticles as template assembly. Journal of Nanoparticle Research 2017, 19 (3) https://doi.org/10.1007/s11051-017-3783-0
- Lingdan Kong, Xiangyang Shi. Functional Dendrimer-Based Vectors for Gene Delivery Applications. 2017,,, 285-309. https://doi.org/10.1007/978-981-10-6059-5_12
- Pratyawadee Singhsa, Hathaikarn Manuspiya, Ravin Narain. Study of the RAFT homopolymerization and copolymerization of N-[3-(dimethylamino)propyl]methacrylamide hydrochloride and evaluation of the cytotoxicity of the resulting homo- and copolymers. Polymer Chemistry 2017, 8 (28) , 4140-4151. https://doi.org/10.1039/C7PY00837F
- Tian Zhou, Yizhou Zhu, Xia Li, Xiangmei Liu, Kelvin W.K. Yeung, Shuilin Wu, Xianbao Wang, Zhenduo Cui, Xianjin Yang, Paul K. Chu. Surface functionalization of biomaterials by radical polymerization. Progress in Materials Science 2016, 83 , 191-235. https://doi.org/10.1016/j.pmatsci.2016.04.005
- Keith H. Parsons, Andrew C. Holley, Gabrielle A. Munn, Alex S. Flynt, Charles L. McCormick. Block ionomer complexes consisting of siRNA and aRAFT-synthesized hydrophilic-block-cationic copolymers II: the influence of cationic block charge density on gene suppression. Polymer Chemistry 2016, 7 (39) , 6044-6054. https://doi.org/10.1039/C6PY01048B
- Jinming Li, Shanshan Xue, Zong-Wan Mao. Nanoparticle delivery systems for siRNA-based therapeutics. Journal of Materials Chemistry B 2016, 4 (41) , 6620-6639. https://doi.org/10.1039/C6TB01462C
- Aditya Ardana, Andrew K. Whittaker, Nigel A.J. McMillan, Kristofer J. Thurecht. Polymeric siRNA delivery vectors: knocking down cancers with polymeric-based gene delivery systems. Journal of Chemical Technology & Biotechnology 2015, 90 (7) , 1196-1208. https://doi.org/10.1002/jctb.4508
- Youliang Zhao, Sébastien Perrier. Reversible Addition-Fragmentation Chain Transfer Polymerization from Surfaces. 2015,,, 77-106. https://doi.org/10.1007/12_2015_316
- Martina Miteva, Kellye C. Kirkbride, Kameron V. Kilchrist, Thomas A. Werfel, Hongmei Li, Christopher E. Nelson, Mukesh K. Gupta, Todd D. Giorgio, Craig L. Duvall. Tuning PEGylation of mixed micelles to overcome intracellular and systemic siRNA delivery barriers. Biomaterials 2015, 38 , 97-107. https://doi.org/10.1016/j.biomaterials.2014.10.036
- Minghui Xu, Junmin Qian, Aili Suo, Weijun Xu, Rongrong Liu, Hongjie Wang. Stimuli-responsive terpolymer mPEG-b-PDMAPMA-b-PAH mediated co-delivery of adriamycin and siRNA to enhance anticancer efficacy. RSC Advances 2015, 5 (27) , 20890-20899. https://doi.org/10.1039/C5RA00348B
- Minghui Xu, Junmin Qian, Aili Suo, Ning Cui, Yu Yao, Weijun Xu, Ting Liu, Hongjie Wang. Co-delivery of doxorubicin and P-glycoprotein siRNA by multifunctional triblock copolymers for enhanced anticancer efficacy in breast cancer cells. Journal of Materials Chemistry B 2015, 3 (10) , 2215-2228. https://doi.org/10.1039/C5TB00031A
- Isil Kurtulus, Gokhan Yilmaz, Muhammed Ucuncu, Mustafa Emrullahoglu, C. Remzi Becer, Volga Bulmus. A new proton sponge polymer synthesized by RAFT polymerization for intracellular delivery of biotherapeutics. Polym. Chem. 2014, 5 (5) , 1593-1604. https://doi.org/10.1039/C3PY01244A
- Andrew C. Holley, Keith H. Parsons, Wenming Wan, Daniel F. Lyons, G. Reid Bishop, John J. Correia, Faqing Huang, Charles L. McCormick. Block ionomer complexes consisting of siRNA and aRAFT-synthesized hydrophilic-block-cationic copolymers: the influence of cationic block length on gene suppression. Polym. Chem. 2014, 5 (24) , 6967-6976. https://doi.org/10.1039/C4PY00940A
- Raviraj Vankayala, Ganesh Gollavelli, Badal Kumar Mandal. Highly fluorescent and biocompatible iridium nanoclusters for cellular imaging. Journal of Materials Science: Materials in Medicine 2013, 24 (8) , 1993-2000. https://doi.org/10.1007/s10856-013-4952-z
- Marya Ahmed, Ravin Narain. Progress of RAFT based polymers in gene delivery. Progress in Polymer Science 2013, 38 (5) , 767-790. https://doi.org/10.1016/j.progpolymsci.2012.09.008
- Alexander H. Stegh. Toward personalized cancer nanomedicine – past, present, and future. Integrative Biology 2013, 5 (1) , 48-65. https://doi.org/10.1039/c2ib20104f
- A. Wei, M. Thomas, J. Mehtala, J. Wang. Gold nanoparticles (GNPs) as multifunctional materials for cancer treatment. 2013,,, 349-389e. https://doi.org/10.1533/9780857096760.3.349
- Seung Jae Lee, Hyeun Hwan An, Hee Soo Kim, Won Bae Han, Chong S. Yoon. Coarsening of Au nanoparticles embedded in solid-supported lipid membrane at 80°C under different humidity. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2012, 409 , 138-142. https://doi.org/10.1016/j.colsurfa.2012.05.050
- Juhee Park, Won Jong Kim. Current status of gene delivery: spotlight on nanomaterial-polymer hybrids. Journal of Drug Targeting 2012, 20 (8) , 648-666. https://doi.org/10.3109/1061186X.2012.704634
- Alexander N. Zelikin, Brigitte Städler. Intelligent Polymer Thin Films and Coatings for Drug Delivery. 2012,,, 243-290. https://doi.org/10.1002/9781118181249.ch7
- T. Musacchio, G. Navarro, V.P. Torchilin. Molecular assemblies for siRNA delivery. Journal of Drug Delivery Science and Technology 2012, 22 (1) , 5-16. https://doi.org/10.1016/S1773-2247(12)50001-8
- Sema Sevimli, Sharon Sagnella, Maria Kavallaris, Volga Bulmus, Thomas P. Davis. Synthesis, self-assembly and stimuli responsive properties of cholesterol conjugated polymers. Polymer Chemistry 2012, 3 (8) , 2057. https://doi.org/10.1039/c2py20112g
- Graeme Moad, Ezio Rizzardo, San H. Thang. Living Radical Polymerization by the RAFT Process – A Third Update. Australian Journal of Chemistry 2012, 65 (8) , 985. https://doi.org/10.1071/CH12295
- Shann S. Yu, Ryan A. Ortega, Brendan W. Reagan, John A. McPherson, Hak‐Joon Sung, Todd D. Giorgio. Emerging applications of nanotechnology for the diagnosis and management of vulnerable atherosclerotic plaques. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 2011, 3 (6) , 620-646. https://doi.org/10.1002/wnan.158
- F.J. Xu, W.T. Yang. Polymer vectors via controlled/living radical polymerization for gene delivery. Progress in Polymer Science 2011, 36 (9) , 1099-1131. https://doi.org/10.1016/j.progpolymsci.2010.11.005
- Karthikeyan Gunasekaran, Thi H. Nguyen, Heather D. Maynard, Thomas P. Davis, Volga Bulmus. Conjugation of siRNA with Comb-Type PEG Enhances Serum Stability and Gene Silencing Efficiency. Macromolecular Rapid Communications 2011, 32 (8) , 654-659. https://doi.org/10.1002/marc.201000804
- Hui Yi Xue, Ho Lun Wong. Tailoring nanostructured solid-lipid carriers for time-controlled intracellular siRNA kinetics to sustain RNAi-mediated chemosensitization. Biomaterials 2011, 32 (10) , 2662-2672. https://doi.org/10.1016/j.biomaterials.2010.12.029
- Paul S. Kim, Shabdis Djazayeri, Reema Zeineldin. Novel nanotechnology approaches to diagnosis and therapy of ovarian cancer. Gynecologic Oncology 2011, 120 (3) , 393-403. https://doi.org/10.1016/j.ygyno.2010.11.029
- Cyrille Boyer, Martina H. Stenzel, Thomas P. Davis. Building nanostructures using RAFT polymerization. Journal of Polymer Science Part A: Polymer Chemistry 2011, 49 (3) , 551-595. https://doi.org/10.1002/pola.24482
- Jae-Hwan Kim, Ji Sun Park, Han Na Yang, Dae Gyun Woo, Su Yeon Jeon, Hyun-Jin Do, Hye-Young Lim, Jung Mo Kim, Keun-Hong Park. The use of biodegradable PLGA nanoparticles to mediate SOX9 gene delivery in human mesenchymal stem cells (hMSCs) and induce chondrogenesis. Biomaterials 2011, 32 (1) , 268-278. https://doi.org/10.1016/j.biomaterials.2010.08.086
- Matthias Barz, Robert Luxenhofer, Rudolf Zentel, María J. Vicent. Overcoming the PEG-addiction: well-defined alternatives to PEG, from structure–property relationships to better defined therapeutics. Polymer Chemistry 2011, 2 (9) , 1900. https://doi.org/10.1039/c0py00406e
- DeeDee Smith, Andrew C. Holley, Charles L. McCormick. RAFT-synthesized copolymers and conjugates designed for therapeutic delivery of siRNA. Polymer Chemistry 2011, 2 (7) , 1428. https://doi.org/10.1039/c1py00038a



