期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 15, 期 -, 页码 6451-6468出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S258906
关键词
vinorelbine; dioscin; non-small cell lung cancer; multi-functional liposomes; tumor microenvironment; MMP2 enzymes
资金
- National Natural Science Foundation of China [81874347, 81703453]
- Liaoning Revitalization Talents Program [XLYC1807132]
- Liaoning Natural Science Foundation [2019-MS-226]
Background: Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse. Purpose: The objective of this study was to construct a novel CPP(mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG(2000)-MAL and CPP-PVGLIG-PEG(5000), to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration. Methods and Results: The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP(mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP(mmp) modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency. Conclusion: CPP(mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.
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