Redox-Responsive, Core-Cross-Linked Micelles Capable of On-Demand, Concurrent Drug Release and Structure Disassembly

• Published in: Biomacromolecules Vol. 14; no. 10; pp. 3706 - 3712
• Main Authors: Wang, Hua, Tang, Li, Tu, Chunlai, Song, Ziyuan, Yin, Qian, Yin, Lichen, Zhang, Zhonghai, Cheng, Jianjun
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14.10.2013
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Applied sciences; Biological and medical sciences; breast neoplasms; Camptothecin - chemical synthesis; Camptothecin - chemistry; Camptothecin - pharmacology; Cell Proliferation - drug effects; Cell Survival - drug effects; Click Chemistry; coprecipitation; Cross-Linking Reagents - chemical synthesis; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - pharmacology; crosslinking; cytotoxicity; dissociation; disulfide bonds; Disulfides - chemistry; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; drugs; Exact sciences and technology; General pharmacology; Humans; MCF-7 Cells; Medical sciences; Micelles; Models, Molecular; Molecular Structure; neoplasm cells; Organic polymers; Oxidation-Reduction; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; polyethylene glycol; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts; Structure-Activity Relationship; Surface Properties; tyrosine; Antineoplastic agent; Ring opening polymerization; 1,3-Dipolar cycloaddition; Triazole derivative copolymer; Propargylic compound; Mixed micelle; Drug carrier; Lactone polymer; Crosslinked copolymer; Chemical reduction; Organic disulfide; Sulfur containing polymer; Tumor cell; Coprecipitation; Release; Amphiphilic polymer; Camptothecin derivatives; Lactone copolymer; Organic azide; Control release polymer; Crosslinking; Prodrug; Ethylene oxide copolymer; Experimental study; In vitro; Biological activity; Chemical modification; Storage stability; Preparation; Diblock copolymer; Kinetics
• DOI: 10.1021/bm401086d
• ISSN: 1525-7797; 1526-4602

We developed camptothecin (CPT)-conjugated, core-cross-linked (CCL) micelles that are subject to redox-responsive cleavage of the built-in disulfide bonds, resulting in disruption of the micellar structure and rapid release of CPT. CCL micelles were prepared via coprecipitation of disulfide-containing CPT-poly(tyrosine(alkynyl)-OCA) conjugate and monomethoxy poly(ethylene glycol)-b-poly(tyrosine(alkynyl)-OCA), followed by cross-linking of the micellar core via azide–alkyne click chemistry. CCL micelles exhibited excellent stability under physiological conditions, while they underwent rapid dissociation in reduction circumstance, resulting in burst release of CPT. These redox-responsive CCL micelles showed enhanced cytotoxicity against human breast cancer cells in vitro.