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Cai, Tongjiang ; Chen, Yangjun ; Wang, Yin ; Wang, Haibo ; Liu, Xiangsheng ; Jin, Qiao ; Agarwal, Seema ; Ji, Jian:
One-Step Preparation of Reduction-Responsive Biodegradable Polymers as Efficient Intracellular Drug Delivery Platforms.
In: Macromolecular Chemistry and Physics.
Bd. 215
(2014)
Heft 19
.
- S. 1848-1854.
ISSN 1521-3935
DOI: https://doi.org/10.1002/macp.201400311
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Angaben zu Projekten
| Projektfinanzierung: |
National Natural Science, Grant Numbers 51333005, 21174126, 51303154, 51025312; National Basic Research Program of China, Grant Number 2011CB606203; Research Fund for the Doctoral Program of Higher Education of China, Grant Numbers 20110101110037, 20120101130013, 20130101120177; Fundamental Research Funds for the Central Universities, Grant Number 2013QNA4047 |
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Abstract
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 × 10−3m 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.