期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 4, 期 8, 页码 1480-1488出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5tb02729b
关键词
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资金
- National Natural Science Foundation of China [21374079, 21244004]
- Program for New Century Excellent Talents in University [NCET-11-1063]
- 131 talents program of Tianjin
- Program for Prominent Young College Teachers of Tianjin Educational Committee
It is still a major challenge for targeted cancer chemotherapy to design a stable biocompatible micellar drug delivery system. To address this dilemma, novel responsive cross-linked micelles (x-micelles) based on polyurethane with photo-responsive coumarin derivatives and pH-responsive hydrazone groups were synthesized. The polymers could be self-assembled into micelles using a typical and facile way. The x-micelles were stable at physiological conditions after UV light induced cross-linking, and can be disassociated under acidic condition. The drug loading content (DLC) and the encapsulation efficiency (EE) of the obtained x-micelles (15.2% and 60.8% respectively) were higher than those of micelles (9.8% and 39.2% respectively), and the DOX release rate of x-micelles was also improved. For targeted therapy, folic acid (FA) was then conjugated to x-micelles, resulting in x-micelles-FA. Cellular viability experiments show that both x-micelles and micelles had a low cytotoxicity and good biocompatibility of up to 1000 mg mL(-1), and DOX-loaded x-micelles-FA and x-micelles exhibited half-maximal inhibitory concentration (IC50) values of 1.17 and 2.40 mu g mL(-1), respectively, to HeLa cells, but have lower cytotoxicity to L929 cells. The pH-responsive x-micelles-FA exhibited superior extracellular stability but activated intracellular drug release. We have demonstrated that the polyurethane with UV- and pH-responsive properties as a novel platform for tumor-targeting drug delivery.
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