期刊
BIOMACROMOLECULES
卷 21, 期 2, 页码 444-453出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.9b01202
关键词
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资金
- National Natural Science Foundation of China [81673022, 81572952, 81373346]
- National Key R and D Program of China [2017YFE0102200]
- National Basic Research Program of China [2014CB931903]
- Zhejiang Provincial Natural Science Foundation of China [LY17H160013]
- Zhejiang Medical and Health Science and Technology Plan Project [2016KYB109]
Self-assembled peptide nanofibers have been widely studied in cancer nanotherapeutics with their excellent biocompatibility and low toxicity of degradation products, showing the significant potential in inhibiting tumor progression. However, poor solubility prevents direct intravenous administration of nanofibers. Although water-soluble peptide precursors have been formed via the method of phosphorylation for intravenous administration, their opportunities for broad in vivo application are limited by the weak capacity of encapsulating drugs. Herein, we designed a novel restructured reduced glutathione (GSH)-responsive drug delivery system encapsulating doxorubicin for systemic administration, which achieved the intracellular restructuration from three-dimensional micelles into one-dimensional nanofibers. After a long blood circulation, micelles endocytosed by tumor cells could degrade in response to high GSH levels, achieving more release and accumulation of doxorubicin at desired sites. Further, the synergistic chemotherapy effects of self-assembled nanofibers were confirmed in both in vitro and in vivo experiments.
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