期刊
POLYMER CHEMISTRY
卷 6, 期 1, 页码 35-43出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4py01123f
关键词
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资金
- Australian Research Council [FT110100411, FS110200025]
- University of Melbourne
- Australian Research Council [FS110200025] Funding Source: Australian Research Council
Nontoxic and acid-degradable cross-linked polymeric vesicles as efficient nanocarriers for the delivery of platinum drugs are reported. Well-defined linear-brush diblock copolymers were synthesized via a robust ring opening metathesis polymerization technique and self-assembled in a selective solvent to form polymeric vesicles with bilayer structure. Vesicles were subsequently cross-linked using acid-degradable diamino ketal cross-linkers and the anticancer drug cis-platin was conjugated to the vesicles with a high loading content (17.6%) through the formation of stable chelate ring structure. This acid-degradable linker leads to a faster drug release in saline under acidic conditions (pH = 5.5) such as those encountered in the late endosome compared to physiological pH (pH = 7.4). Cancer cells tended to readily internalize the vesicles and dose-response cytotoxicity studies suggested that the drug-loaded cross-linked vesicles were more efficient in delivering the platinum drug into cancer cells compared to internalization of the free drug. Additionally, polymer vesicles prior to platinum conjugation were nontoxic towards cancer cells.
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