One-Step Preparation of Reduction-Responsive Biodegradable Polymers as Efficient Intracellular Drug Delivery Platforms

被引:19
作者
Cai, Tongjiang [1 ]
Chen, Yangjun [1 ]
Wang, Yin [1 ]
Wang, Haibo [1 ]
Liu, Xiangsheng [1 ]
Jin, Qiao [1 ]
Agarwal, Seema [2 ]
Ji, Jian [1 ]
机构
[1] Zhejiang Univ, MOE Key Lab Macromol Synth & Functionalizat, Minist Educ, Dept Polymer Sci & Engn, Hangzhou 310027, Peoples R China
[2] Univ Bayreuth, Bayreuth Ctr Colloids & Interfaces, D-95440 Bayreuth, Germany
基金
中国国家自然科学基金; 高等学校博士学科点专项科研基金;
关键词
biodegradable; drug release; 2-methylene-1; 3-dioxepane (MDO); reduction-responsive; RING-OPENING POLYMERIZATION; BLOCK-COPOLYMERS; NANOPARTICLES; MICELLES; PH; ASSEMBLIES; CHEMISTRY; 2-METHYLENE-1,3-DIOXEPANE; FUNCTIONALIZATION; POLYESTERS;
D O I
10.1002/macp.201400311
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
Reduction-responsive biodegradable polymeric micelles based on functional 2-methylene-1,3-dioxepane (MDO) copolymers are developed and investigated for triggered doxorubicin (DOX) release. The MDO-based copolymers P(MDO-co-PEGMA-co-PDSMA) are synthesized via the simple one-step radical ring-opening copolymerization of MDO, poly(ethylene glycol) methyl ether methacrylate (PEGMA), and pyridyldisulfide ethylmethacrylate (PDSMA). The copolymers can self-assemble to form micelles in aqueous solution. DOX, a model anticancer drug, is loaded into the micelles with the drug loading content (DLC) of 11.3%. The micelles can be disassembled under a reductive environment (10 x 10(-3)m glutathione), which results in a triggered drug release behavior. The glutathione-mediated intracellular drug release of DOX-loaded micelles is investigated against A549 cells. Confocal laser scanning microscopy (CLSM) results demonstrated that DOX-loaded micelles exhibits faster drug release in glutathione monoester (GSH-OEt)-pretreated A549 cells, compared with untreated and buthionine sulfoximine (BSO)-pretreated A549 cells. Based on the facile synthetic strategy, the reduction-sensitive biodegradable micelles with triggered intracellular drug release are promising for anticancer drug delivery.
引用
收藏
页码:1848 / 1854
页数:7
相关论文
共 39 条
[2]   Biodegradable Nanoparticles as Vaccine Adjuvants and Delivery Systems: Regulation of Immune Responses by Nanoparticle-Based Vaccine [J].
Akagi, Takami ;
Baba, Masanori ;
Akashi, Mitsuru .
POLYMERS IN NANOMEDICINE, 2012, 247 :31-64
[3]  
Aliabadi Hamidreza Montazeri, 2006, Expert Opin Drug Deliv, V3, P139
[4]  
BAILEY WJ, 1982, MAKROMOL CHEM, V183, P1913
[5]   Stimuli-Responsive Polymers and Their Applications in Nanomedicine [J].
Cabane, Etienne ;
Zhang, Xiaoyan ;
Langowska, Karolina ;
Palivan, Cornelia G. ;
Meier, Wolfgang .
BIOINTERPHASES, 2012, 7 (1-4) :1-27
[6]   Functional 2-methylene-1,3-dioxepane terpolymer: a versatile platform to construct biodegradable polymeric prodrugs for intracellular drug delivery [J].
Cai, Tongjiang ;
Chen, Yangjun ;
Wang, Yin ;
Wang, Haibo ;
Liu, Xiangsheng ;
Jin, Qiao ;
Agarwal, Seema ;
Ji, Jian .
POLYMER CHEMISTRY, 2014, 5 (13) :4061-4068
[7]   Fabrication of star-shaped, thermo-sensitive poly(N-isopropylacrylamide)-cholic acid-poly(ε-caprolactone) copolymers and their self-assembled micelles as drug carriers [J].
Chen, Wen-Qin ;
Wei, Hua ;
Li, Song-Lin ;
Feng, Jun ;
Nie, Jun ;
Zhang, Xian-Zheng ;
Zhuo, Ren-Xi .
POLYMER, 2008, 49 (18) :3965-3972
[8]   Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery [J].
Cheng, Ru ;
Meng, Fenghua ;
Deng, Chao ;
Klok, Harm-Anton ;
Zhong, Zhiyuan .
BIOMATERIALS, 2013, 34 (14) :3647-3657
[9]   Reduction-responsive cross-linked micelles based on PEGylated polypeptides prepared via click chemistry [J].
Cheng, Yilong ;
He, Chaoliang ;
Xiao, Chunsheng ;
Ding, Jianxun ;
Ren, Kaixuan ;
Yu, Shuangjiang ;
Zhuang, Xiuli ;
Chen, Xuesi .
POLYMER CHEMISTRY, 2013, 4 (13) :3851-3858
[10]   Doxorubicin-Loaded Nanogel Assemblies with pH/Thermo-triggered Payload Release for Intracellular Drug Delivery [J].
Chiang, Wen-Hsuan ;
Huang, Wen-Chia ;
Chang, Yu-Jen ;
Shen, Ming-Yin ;
Chen, Hsin-Hung ;
Chern, Chorng-Shyan ;
Chiu, Hsin-Cheng .
MACROMOLECULAR CHEMISTRY AND PHYSICS, 2014, 215 (13) :1332-1341