基于炔烃参与的多组分聚合构建氧化还原双重响应型高分子药物载体

何俊男; 郑玉斌; 郑楠

doi:10.11777/j.issn1000-3304.2021.21054

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基于炔烃参与的多组分聚合构建氧化还原双重响应型高分子药物载体

研究论文 | 更新时间：2023-12-20

- 基于炔烃参与的多组分聚合构建氧化还原双重响应型高分子药物载体
- Preparation of Drug Carriers with Dual Redox-responsibility via Multicomponent Polymerization of Alkynes
- 高分子学报 2021年52卷第10期页码：1298-1307
- 作者机构：
  
  大连理工大学化工学院大连 116023
- 作者简介：
  
  E-mail: nzheng@dlut.edu.cn
- 基金信息：
  
  国家自然科学基金(基金号 51703018);中央引导地方科技发展专项资金(2021JH6/10500148)
- DOI：10.11777/j.issn1000-3304.2021.21054
  中图分类号：
- 纸质出版日期：2021-10-20，
  
  网络出版日期：2021-08-11，
  
  收稿日期：2021-02-22，
  
  修回日期：2021-04-30，
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何俊男,郑玉斌,郑楠.基于炔烃参与的多组分聚合构建氧化还原双重响应型高分子药物载体[J].高分子学报,2021,52(10):1298-1307.

He Jun-nan,Zheng Yu-bin,Zheng Nan.Preparation of Drug Carriers with Dual Redox-responsibility via Multicomponent Polymerization of Alkynes[J].ACTA POLYMERICA SINICA,2021,52(10):1298-1307.
何俊男,郑玉斌,郑楠.基于炔烃参与的多组分聚合构建氧化还原双重响应型高分子药物载体[J].高分子学报,2021,52(10):1298-1307. DOI： 10.11777/j.issn1000-3304.2021.21054.

He Jun-nan,Zheng Yu-bin,Zheng Nan.Preparation of Drug Carriers with Dual Redox-responsibility via Multicomponent Polymerization of Alkynes[J].ACTA POLYMERICA SINICA,2021,52(10):1298-1307. DOI： 10.11777/j.issn1000-3304.2021.21054.

摘要

为了拓展多组分聚合方法在药物载体领域应用，基于铜催化的炔烃多组分聚合设计合成含有二硒键的氧化还原响应型两亲性聚合物，与阿霉素(DOX)在水溶液中通过自组装方式构建纳米载药胶束. 通过实验技术手段对纳米载药胶束表征可知，纳米载药胶束的粒径在130 nm左右，临界胶束浓度(CMC)值为0.23 mg/mL，在人体正常生理条件下结构稳定. 肿瘤中含有浓度较高的活性氧(ROS)或谷胱甘肽(GSH)，聚合物主链中二硒键在氧化还原条件下断裂，导致聚合物降解，DOX从纳米载药胶束中逐渐释放，且累积释放量可达100%，并发现该类载药胶束在GSH环境中药物释放性能优于ROS环境. 该工作通过多组分聚合方式可以便捷构建氧化还原双重响应型的两亲性聚合物，在肿瘤微环境中表现出特异的降解性能，为开发设计智能响应型高分子药物载体提供新的思路.

Abstract

Multicomponent polymerization (MCP) has the advantages of high reaction efficiency

mild reaction conditions

high atomic economy and facile operation

which is a new trend in constructing complex and functional polymers. In order to explore the application of MCP in the design of drug delivery carriers

in this work

a dual redox-responsive amphiphilic polymer containing diselenide bonds was synthesized based on copper-catalyzed MCP. Amphiphilic polymer and doxorubicin (DOX) were used to construct drug-loaded nano micelles through self-assembly in aqueous solution. The characterization of the micelles shows that the particle size is about 130 nm

and the critical micelle concentration (CMC) value is 0.23 mg/mL. Under normal physiological conditions

the nano micelles remain structurally stable. However

in a tumor environment containing reactive oxygen species (ROS) or glutathione (GSH)

DOX is released from the nano drug-loaded micelles

and the cumulative release amount of DOX reaches 100%. The main reason for this result is that the diselenide bond in the polymer backbone is cleaved under redox conditions. It is found that nano drug-loaded micelles have better drug release performance in the GSH environment than those in the ROS environment. Studies have shown that the redox-responsive amphiphilic polymer is conveniently constructed through MCP

and the polymer exhibits specific degradation properties in the tumor microenvironment. This work provides a new idea for the development and design of intelligent nano drug-loaded micelles.

关键词

多组分聚合氧化还原型两亲性聚合物载药胶束二硒

Keywords

Multicomponent polymerizationRedoxAmphiphilic polymerDrug-loaded micellesDiselenide

references

Danhier F, Feron O, Préat V. J Control Release, 2010, 148(2): 135-146. doi:10.1016/j.jconrel.2010.08.027http://dx.doi.org/10.1016/j.jconrel.2010.08.027

Ahn J, Miura Y, Yamada N, Chida T, Liu X, Kim A, Sato R, Tsumura R, Koga Y, Yasunaga M, Nishiyama N,Matsumura Y, Cabral H, Kataoka K. Biomaterials, 2015, 39: 23-30. doi:10.1016/j.biomaterials.2014.10.069http://dx.doi.org/10.1016/j.biomaterials.2014.10.069

Zhu W W, Dong Z L, Fu T T, Liu J J, Chen Q, Li Y G, Zhu R, Xu L G, Li Z. Adv Funct Mater, 2016, 26: 5490-5498. doi:10.1002/adfm.201600676http://dx.doi.org/10.1002/adfm.201600676

Chiang Y T, Lo C L. Biomaterials, 2014, 35(20): 5414-5424. doi:10.1016/j.biomaterials.2014.03.046http://dx.doi.org/10.1016/j.biomaterials.2014.03.046

Zhou Z, Li L, Yang Y, Xu X L, Huang Y. Biomaterials, 2014, 35(24): 6622-6635. doi:10.1016/j.biomaterials.2014.04.059http://dx.doi.org/10.1016/j.biomaterials.2014.04.059

Tian Z M, Liu H B, Guo Z X, Gou W Y, Liang Z C, Qu Y Q, Han L L, Liu L. Small, 2020, 16(47): 2004654. doi:10.1002/smll.202004654http://dx.doi.org/10.1002/smll.202004654

Xu X D, Saw P E, Tao W, Li Y J, Ji X Y, Bhasin S, Liu Y L, Ayyash D, Rasmussen J, Huo M, Shi J J, Farokhzad O C. Adv Mater, 2017, 29(33): 1702311. doi:10.1002/adma.201700141http://dx.doi.org/10.1002/adma.201700141

Chen Yiming(陈艺铭), Qi Yu(祁宇), Hu Wenting(胡文婷), Zheng Di(郑迪), Yu Bingran(俞丙然), Xu Fujiang(徐福建). Acta Polymerica Sinica(高分子学报), 2019, 50(6): 602-612

Liu F R, Gong S L, Shen M L, He T, Liang X Q, Shu Y Q, Wang X X, Ma S, Li X C, Zhang M M, Wu Q J, Gong C Y. Chem Eng J, 2021, 403: 126305-126309. doi:10.1016/j.cej.2020.126305http://dx.doi.org/10.1016/j.cej.2020.126305

Shahriari M, Zahiri M, Abnous K, Taghdisi S M, Ramezani M, Alibolandi M. J Control Release, 2019, 308: 172-189. doi:10.1016/j.jconrel.2019.07.004http://dx.doi.org/10.1016/j.jconrel.2019.07.004

Zhang Y L, Han X X, Nie G J. Nat Protoc, 2021, 16: 405-430. doi:10.1038/s41596-020-00421-0http://dx.doi.org/10.1038/s41596-020-00421-0

Shi C, Li M L, Zhang Z, Yao Q C, Shao K, Xu F, Xu N, Li H D, Fan J L, Sun W, Du J J, Long S R, Wang J Y, Peng X J. Biomaterials, 2020, 233: 119755. doi:10.1016/j.biomaterials.2020.119755http://dx.doi.org/10.1016/j.biomaterials.2020.119755

Sun P P, Jia L, Hai J, Lu S Y, Chen F J, Liang K, Sun S H, Liu H W, Fu X, Zhu Y H, Wang B D. Adv Healthc Mater, 2020, 10(4): 2001728. doi:10.1002/adhm.202001728http://dx.doi.org/10.1002/adhm.202001728

Cao W, Zhang X L, Miao X M, Yang Z M, Xu H P. Angew Chem Int Ed, 2013, 52(24): 6233-6237. doi:10.1002/anie.201300662http://dx.doi.org/10.1002/anie.201300662

Sun T B, Jin Y, Qi R, Peng S J, Fan B Z. Polym Chem, 2013, 4(14): 4017-4023. doi:10.1039/c3py00406fhttp://dx.doi.org/10.1039/c3py00406f

Fan C W, Ding C L, Pan X Q, Zhang Z B, Zhu J, Zhu X L. Macromol Rapid Commun, 2015, 36(10): 903-908. doi:10.1002/marc.201500034http://dx.doi.org/10.1002/marc.201500034

Deepagan V G, Kwon S, You D G, Nguyen V Q, Um W, Ko H, Lee H, Jo D G, Kang Y M, Park J H. Biomaterials, 2016, 103: 56-66. doi:10.1016/j.biomaterials.2016.06.044http://dx.doi.org/10.1016/j.biomaterials.2016.06.044

Xia J H, Ji S B, Xu H P. Polym Chem, 2016, 7(44): 6708-6713. doi:10.1039/c6py01610chttp://dx.doi.org/10.1039/c6py01610c

Sun C X, Ji S B, Li F, Xu H P. ACS Appl Mater Interfaces, 2017, 9(15): 12924-12929. doi:10.1021/acsami.7b02367http://dx.doi.org/10.1021/acsami.7b02367

Won H J, Ryplida B, Kim S G, Lee G, Ryu J H, Park S Y. ACS Nano, 2020, 14(7): 8409-8420. doi:10.1021/acsnano.0c02517http://dx.doi.org/10.1021/acsnano.0c02517

Xia Jiahao(夏嘉豪), Tang Yizheng(谭以正), Xu Huaping(许华平). Acta Polymerica Sinica(高分子学报), 2020, 51(11): 1190-1200

Ma N, Li Y, Xu H P, Wang Z Q, Zhang X. J Am Chem Soc, 2010, 132(2): 442-443. doi:10.1021/ja908124ghttp://dx.doi.org/10.1021/ja908124g

Zhang L S, Liu Y C, Zhang K, Chen Y W, Luo X L. Colloid Polym Sci, 2019, 297(2): 225-238. doi:10.1007/s00396-018-4457-xhttp://dx.doi.org/10.1007/s00396-018-4457-x

Choi S Y, Huh K M, Shim M S, Park I S, Cho Y Y, Lee J Y, Lee H S, Kang H C. Adv Funct Mater, 2020, 31(6): 2007275. doi:10.1002/adfm.202007275http://dx.doi.org/10.1002/adfm.202007275

Zuo X J, Sun B J, Yang Y X, Zhou S, Zhang Y, Guo M R, Sun M C, Luo C, He Z G, Sun J. Small, 2020, 16: 2005039 10.1002/adfm.202007275http://dx.doi.org/10.1002/adfm.202007275

Yang J C, Pan S J, Gao S Q, Li T Y, Xu H P. Biomaterials, 2021, 271: 120721. doi:10.1016/j.biomaterials.2021.120721http://dx.doi.org/10.1016/j.biomaterials.2021.120721

Kakuchi R. Angew Chem Int Ed, 2014, 53(1): 46-48. doi:10.1002/anie.201305538http://dx.doi.org/10.1002/anie.201305538

Stiernet P, Lecomte P, De W J, Debuigne A. ACS Macro Lett, 2019, 8(4): 427-434. doi:10.1021/acsmacrolett.9b00182http://dx.doi.org/10.1021/acsmacrolett.9b00182

Hartweg M, Becer C R. Green Chem, 2016, 18(11): 3272-3277. doi:10.1039/c6gc00372ahttp://dx.doi.org/10.1039/c6gc00372a

Deng X X, Li L, Li Z L, Lv A, Du F S, Li Z C. ACS Macro Lett, 2012, 1(11): 1300-1303. doi:10.1021/mz300456phttp://dx.doi.org/10.1021/mz300456p

Li L, Lv A, Deng X X, Du F S, Li Z C. Chem Commun, 2013, 49(76): 8549-8551. doi:10.1039/c3cc44557ghttp://dx.doi.org/10.1039/c3cc44557g

Cui Y, Zhang M, Du F S, Li Z C. ACS Macro Lett, 2017, 6(1): 11-35. doi:10.1021/acsmacrolett.6b00833http://dx.doi.org/10.1021/acsmacrolett.6b00833

Lee I H, Kim H, Choi T L. J Am Chem Soc, 2013, 135(10): 3760-3764. doi:10.1021/ja312592ehttp://dx.doi.org/10.1021/ja312592e

Kim H, Choi T L. ACS Macro Lett, 2014, 3(8): 791-794. doi:10.1021/mz5003239http://dx.doi.org/10.1021/mz5003239

Deng H Q, Zhao E G, Li H K, Lam J W Y, Tang B Z. Macromolecules, 2015, 48(10): 3180-3189. doi:10.1021/acs.macromol.5b00644http://dx.doi.org/10.1021/acs.macromol.5b00644

Deng H Q, Han T, Zhao E G, Kwok R T K, Lam J W Y, Tang B Z. Polym Chem, 2016, 7(36): 5646-5654. doi:10.1039/c6py01337fhttp://dx.doi.org/10.1039/c6py01337f

Deng H Q, Han T, Zhao E G, Kwok R T K, Lam J W Y, Tang B Z. Macromolecules, 2016, 49: 5475-5483. doi:10.1021/acs.macromol.6b01217http://dx.doi.org/10.1021/acs.macromol.6b01217

Xu L G, Hu R R, Tang B Z. Macromolecules 2017, 50(16): 6043-6053. doi:10.1021/acs.macromol.7b01096http://dx.doi.org/10.1021/acs.macromol.7b01096

Han T, Deng H, Qiu Z, Zhao Z, Zhang H, Zou H, Leung N L C, Shan G, Elsegood M R J, Lam J W Y, Tang B Z. J Am Chem Soc, 2018, 140(16): 5588-5598. doi:10.1021/jacs.8b01991http://dx.doi.org/10.1021/jacs.8b01991

Xu L G, Zhou T T, Liao M, Hu R R, Tang B Z. ACS Macro Lett, 2019, 8(2): 101-106. doi:10.1021/acsmacrolett.8b00884http://dx.doi.org/10.1021/acsmacrolett.8b00884

Kim H, Bang, K T, Choi I, Lee J K, Choi T L. J Am Chem Soc, 2016, 138(27): 8612-8622. doi:10.1021/jacs.6b04695http://dx.doi.org/10.1021/jacs.6b04695

He J N, Zheng N, Xie D, Zheng Y B, Song W Z. Polym Chem, 2020, 11(6): 1198-1210. doi:10.1039/c9py01576khttp://dx.doi.org/10.1039/c9py01576k

Ma G H, Liu J, He J L, Zhang M Z, Ni P H. ACS Biomater Sci Eng, 2018, 4(7): 2443-2452. doi:10.1021/acsbiomaterials.8b00429http://dx.doi.org/10.1021/acsbiomaterials.8b00429

Lu W H, Xu X X, Imbernon L, Zhu J, Hoogenboom R, Prez F E D, Pan X Q. Biomacromolecules, 2020, 21(8): 3308-3317. doi:10.1021/acs.biomac.0c00762http://dx.doi.org/10.1021/acs.biomac.0c00762

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