期刊
POLYMER CHEMISTRY
卷 4, 期 11, 页码 3345-3356出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3py00144j
关键词
-
资金
- National Natural Science Foundation of China [51233004, 51273196, 51273037, 51203153, 51273080, 51103015, 51021003, 20904053, 21174142]
A series of thermo-responsive hairy-rod polypeptides was efficiently synthesized by grafting of azide-terminated (co)polymers of 2-(2-methoxyethoxy)ethyl methacrylate (MEO(2)MA) or 2-(2-(2-methoxyethoxy) ethoxy) ethyl methacrylate (MEO(3)MA) (i.e., N-3-PMEOiMA) onto poly(gamma-propargyl-L-glutamate) (PPLG) through a click reaction. The thermo-responsiveness and secondary structure of the resultant polypeptides (i.e. PLG-g-PMEO(i)MA) were shown to be dependent on the MEO2MA : MEO3MA ratio in PMEO(i)MA side chains. PLG(40)-g-P(MEO(2)MA(18)-co-MEO(3)MA(9)) (P2) and PLG40-g-P(MEO(2)MA(7)-co-MEO(3)MA(18)) (P4) with lower critical solution temperatures at 25.6 and 34.8 degrees C, and cloud points at 26.9 and 35.6 degrees C in physiological saline, respectively, were selected to self-assemble into micelles for doxorubicin (DOX) loading and release. In vitro DOX release from DOX-loaded micelles could be accelerated by a decrease of temperature and pH. Confocal laser scanning microscopy and flow cytometry confirmed the efficient internalization and intracellular DOX release of DOX-loaded micelles towards HeLa cells (a human cervical carcinoma cell line). In vitro methyl thiazolyl tetrazolium assays revealed that the polypeptides were cytocompatible, and DOX-loaded micelles showed efficient cellular proliferation inhibition. Hemolysis tests indicated that micelles were hemocompatible, and the encapsulation with polypeptides significantly reduced the hemolysis ratio of DOX. Therefore, the thermo-responsive polypeptide micelles, which are stable in physiological condition while releasing payloads in the acidic intracellular microenvironment, are promising for smart drug delivery.
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