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

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.