title: Development of Long-Circulating Zwitterionic Cross-Linked Micelles for Active-Targeted Drug Delivery.
abstract: Blood stability, active targeting, and controlled drug release are the most important features to design desirable drug carriers. Here, we demonstrate a zwitterionic biodegradable cross-linked micelle based on a penta-block copolymer, which utilizes poly(carboxybetaine methacrylate) as hydrophilic segment, poly(ε-caprolactone) as biodegradable hydrophobic segment, poly(S-2-hydroxyethyl-O-ethyl dithiocarbonate methacrylate) (PSODMA) block as thiol protecting segment for cross-linking, and cyclic Arg-Gly-Asp-d-Tyr-Lys [c(RGDyK)] as targeting ligand. As a result, this micelle possessed excellent colloidal stability at high dilution and in 50% fetal bovine serum. In vitro drug release experiment showed no burst release under physiological conditions but accelerated drug release in mimicking tumor tissue environment. In vivo tests showed that the drug-loaded micelles had prolonged half-life in bloodstream, enhanced therapeutic efficiency, and reduced cardiac toxicity and biotoxicity compared with free drug formulation. Taken together, the reported c(RGDyK)-modified zwitterionic interfacially cross-linked micelle has emerged as an appealing platform for cancer therapy.
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University , Hangzhou, Zhejiang 310027, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Lin
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University , Hangzhou, Zhejiang 310027, China.
authors.forename: Guanglong
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Materials and Interfaces, Weizmann Institute of Science , Rehovot 7610001, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Kampf
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University , Hangzhou, Zhejiang 310027, China.
authors.forename: Zhefan
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University , Hangzhou, Zhejiang 310027, China.|Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biomedical Materials, College of Chemistry and Materials Science, Nanjing Normal University , Nanjing 210046, China.
authors.forename: Shengfu
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005260:Female; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D010456:Peptides, Cyclic / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D008823:Micelles; D010456:Peptides, Cyclic; D011108:Polymers; D004317:Doxorubicin