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Thermoresponsive Polymer Micelles as Potential Nanosized Cancerostatics

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Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Department of Biomedical Polymers, Heyrovský square 2, 162 06 Prague, Czech Republic
*E-mail: [email protected]
Cite this: Biomacromolecules 2015, 16, 8, 2493–2505
Publication Date (Web):July 8, 2015
https://doi.org/10.1021/acs.biomac.5b00764
Copyright © 2015 American Chemical Society
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Abstract

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An effective chemotherapy for neoplastic diseases requires the use of drugs that can reach the site of action at a therapeutically efficacious concentration and maintain it at a constant level over a sufficient period of time with minimal side effects. Currently, conjugates of high-molecular-weight hydrophilic polymers or biocompatible nanoparticles with stimuli-releasable anticancer drugs are considered to be some of the most promising systems capable of fulfilling these criteria. In this work, conjugates of thermoresponsive diblock copolymers with the covalently bound cancerostatic drug pirarubicin (PIR) were synthesized as a reversible micelle-forming drug delivery system combining the benefits of the above-mentioned carriers. The diblock copolymer carriers were composed of hydrophilic poly[N-(2-hydroxypropyl)methacrylamide]-based block containing a small amount (∼5 mol %) of comonomer units with reactive hydrazide groups and a thermoresponsive poly[2-(2-methoxyethoxy)ethyl methacrylate] block. PIR was attached to the hydrophilic block of the copolymer through the pH-sensitive hydrazone bond designed to be stable in the bloodstream at pH 7.4 but to be degraded in an intratumoral/intracellular environment at pH 5–6. The temperature-induced conformation change of the thermoresponsive block (coil–globule transition), followed by self-assembly of the copolymer into a micellar structure, was controlled by the thermoresponsive block length and PIR content. The cytotoxicity and intracellular transport of the conjugates as well as the release of PIR from the conjugates inside the cells, followed by its accumulation in the cell nuclei, were evaluated in vitro using human colon adenocarcinoma (DLD-1) cell lines. It was demonstrated that the studied conjugates have a great potential to become efficacious in vivo pharmaceuticals.

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The Supporting Information shows chemical structures of the polymer conjugates PC5 and PC6, examples of the detailed SEC profiles for the polymers PP2 and PC2, and comparison ot the temperature dependences of the polymer conjugate PC2 before and after hydrolysis. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biomac.5b00764.

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Cited By

This article is cited by 27 publications.

  1. Xing Wang, Yanyu Yang, Yaping Zhuang, Peiyuan Gao, Fei Yang, Hong Shen, Hongxia Guo, and Decheng Wu . Fabrication of pH-Responsive Nanoparticles with an AIE Feature for Imaging Intracellular Drug Delivery. Biomacromolecules 2016, 17 (9) , 2920-2929. https://doi.org/10.1021/acs.biomac.6b00744
  2. Sergey K. Filippov, Anna Bogomolova, Leonid Kaberov, Nadiia Velychkivska, Larisa Starovoytova, Zulfiya Cernochova, Sarah E. Rogers, Wing Man Lau, Vitaliy V. Khutoryanskiy, and Michael T. Cook . Internal Nanoparticle Structure of Temperature-Responsive Self-Assembled PNIPAM-b-PEG-b-PNIPAM Triblock Copolymers in Aqueous Solutions: NMR, SANS, and Light Scattering Studies. Langmuir 2016, 32 (21) , 5314-5323. https://doi.org/10.1021/acs.langmuir.6b00284
  3. Alena Braunová, Petr Chytil, Richard Laga, Milada Šírová, Daniela Machová, Jozef Parnica, Blanka Říhová, Olga Janoušková, Tomáš Etrych. Polymer nanomedicines based on micelle-forming amphiphilic or water-soluble polymer-doxorubicin conjugates: Comparative study of in vitro and in vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties. Journal of Controlled Release 2020, 321 , 718-733. https://doi.org/10.1016/j.jconrel.2020.03.002
  4. Shannon M. North, Steven P. Armes. Aqueous solution behavior of stimulus-responsive poly(methacrylic acid)-poly(2-hydroxypropyl methacrylate) diblock copolymer nanoparticles. Polymer Chemistry 2020, 11 (12) , 2147-2156. https://doi.org/10.1039/D0PY00061B
  5. Rafał Konefał, Jiří Spěváček, Gabriela Mužíková, Richard Laga. Thermoresponsive behavior of poly(DEGMA)-based copolymers. NMR and dynamic light scattering study of aqueous solutions. European Polymer Journal 2020, 124 , 109488. https://doi.org/10.1016/j.eurpolymj.2020.109488
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  7. Geoffrey M. Lynn, Richard Laga, Christopher M. Jewell. Induction of anti-cancer T cell immunity by in situ vaccination using systemically administered nanomedicines. Cancer Letters 2019, 459 , 192-203. https://doi.org/10.1016/j.canlet.2019.114427
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  10. Prajakta Tambe, Pramod Kumar, Kishore M. Paknikar, Virendra Gajbhiye. Smart triblock dendritic unimolecular micelles as pioneering nanomaterials: Advancement pertaining to architecture and biomedical applications. Journal of Controlled Release 2019, 299 , 64-89. https://doi.org/10.1016/j.jconrel.2019.02.026
  11. Ye Tian, Ying Liu, Benzhi Ju, Xiaozhong Ren, Mingyun Dai. Thermoresponsive 2-hydroxy-3-isopropoxypropyl hydroxyethyl cellulose with tunable LCST for drug delivery. RSC Advances 2019, 9 (4) , 2268-2276. https://doi.org/10.1039/C8RA09075K
  12. Debabrata Ghosh Dastidar, Gopal Chakrabarti. Thermoresponsive Drug Delivery Systems, Characterization and Application. 2019,,, 133-155. https://doi.org/10.1016/B978-0-12-814029-1.00006-5
  13. Ali Alsuraifi, Anthony Curtis, Dimitrios Lamprou, Clare Hoskins. Stimuli Responsive Polymeric Systems for Cancer Therapy. Pharmaceutics 2018, 10 (3) , 136. https://doi.org/10.3390/pharmaceutics10030136
  14. Duo Wei, Lingling Ge, Rong Guo. Effect of hydrophilically modified ibuprofen on thermoresponsive gelation of pluronic copolymer. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2018, 553 , 1-10. https://doi.org/10.1016/j.colsurfa.2018.05.012
  15. Michal Pechar, Robert Pola, Olga Janoušková, Irena Sieglová, Vlastimil Král, Milan Fábry, Barbora Tomalová, Marek Kovář. Polymer Cancerostatics Targeted with an Antibody Fragment Bound via a Coiled Coil Motif: In Vivo Therapeutic Efficacy against Murine BCL1 Leukemia. Macromolecular Bioscience 2018, 18 (1) , 1700173. https://doi.org/10.1002/mabi.201700173
  16. Petr Chytil, Eva Koziolová, Tomáš Etrych, Karel Ulbrich. HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release. Macromolecular Bioscience 2018, 18 (1) , 1700209. https://doi.org/10.1002/mabi.201700209
  17. Katerina Goracinova, Nikola Geskovski, Simona Dimchevska, Xue Li, Ruxandra Gref. Multifunctional core–shell polymeric and hybrid nanoparticles as anticancer nanomedicines. 2018,,, 109-160. https://doi.org/10.1016/B978-0-12-813669-0.00004-X
  18. Hui Wang, Qianwang Chen, Shuiqin Zhou. Carbon-based hybrid nanogels: a synergistic nanoplatform for combined biosensing, bioimaging, and responsive drug delivery. Chemical Society Reviews 2018, 47 (11) , 4198-4232. https://doi.org/10.1039/C7CS00399D
  19. Sanjay Kumar Jain, Ankita Tiwari, Ankit Jain, Amit Verma, Shivani Saraf, Pritish Kumar Panda, Gaytri Gour. Application Potential of Polymeric Nanoconstructs for Colon-Specific Drug Delivery. 2018,,, 22-49. https://doi.org/10.4018/978-1-5225-4781-5.ch002
  20. Kaila P. Medina-Alarcón, Aline R. Voltan, Bruno Fonseca-Santos, Isabela Jacob Moro, Felipe de Oliveira Souza, Marlus Chorilli, Christiane Pienna Soares, André Gonzaga dos Santos, Maria J.S. Mendes-Giannini, Ana M. Fusco-Almeida. Highlights in nanocarriers for the treatment against cervical cancer. Materials Science and Engineering: C 2017, 80 , 748-759. https://doi.org/10.1016/j.msec.2017.07.021
  21. Thiruganesh Ramasamy, Hima Bindu Ruttala, Biki Gupta, Bijay Kumar Poudel, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim. Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review. Journal of Controlled Release 2017, 258 , 226-253. https://doi.org/10.1016/j.jconrel.2017.04.043
  22. Mingjun Zhou, Yulia Shmidov, John B. Matson, Ronit Bitton. Multi-scale characterization of thermoresponsive dendritic elastin-like peptides. Colloids and Surfaces B: Biointerfaces 2017, 153 , 141-151. https://doi.org/10.1016/j.colsurfb.2017.02.014
  23. Aishun Ding, Guolin Lu, Hao Guo, Xiaoyu Huang. Polyallene-based amphiphilic triblock copolymer via successive free radical polymerization and ATRP. Polymer Chemistry 2017, 8 (48) , 7537-7545. https://doi.org/10.1039/C7PY01407D
  24. Xufeng Zhou, Cong Chang, Yang Zhou, Lu Sun, Hua Xiang, Sijie Zhao, Liwei Ma, Guohua Zheng, Mingzhu Liu, Hua Wei. A comparison study to investigate the effect of the drug-loading site on its delivery efficacy using double hydrophilic block copolymer-based prodrugs. Journal of Materials Chemistry B 2017, 5 (23) , 4443-4454. https://doi.org/10.1039/C7TB00261K
  25. Robert Pola, Anne-Kathrin Heinrich, Thomas Mueller, Libor Kostka, Karsten Mäder, Michal Pechar, Tomas Etrych. Passive Tumor Targeting of Polymer Therapeutics: In Vivo Imaging of Both the Polymer Carrier and the Enzymatically Cleavable Drug Model. Macromolecular Bioscience 2016, 16 (11) , 1577-1582. https://doi.org/10.1002/mabi.201600273
  26. Tomáš Etrych, Henrike Lucas, Olga Janoušková, Petr Chytil, Thomas Mueller, Karsten Mäder. Fluorescence optical imaging in anticancer drug delivery. Journal of Controlled Release 2016, 226 , 168-181. https://doi.org/10.1016/j.jconrel.2016.02.022
  27. Jianbo Tan, Yuhao Bai, Xuechao Zhang, Li Zhang. Room temperature synthesis of poly(poly(ethylene glycol) methyl ether methacrylate)-based diblock copolymer nano-objects via Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA). Polymer Chemistry 2016, 7 (13) , 2372-2380. https://doi.org/10.1039/C6PY00022C

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