期刊
ADVANCED SCIENCE
卷 7, 期 17, 页码 -出版社
WILEY
DOI: 10.1002/advs.201902746
关键词
membrane type 1-matrix metalloproteinase-activated cilengitide; pancreatic cancer; smart liposomes; vascular promotion
资金
- National Natural Science Foundation of China [81703010, 81872428]
- China Postdoctoral Science Foundation [2016M600342]
- National Key Research and Development Program of China [NBHY-2017-J1-3]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDA15014200]
Promoting tumor angiogenesis effectively and specifically to resolve tumor-associated hypoperfusion holds promise for improving pancreatic cancer therapy. Herein, a doxorubicin (DOX) loaded smart liposome, MC-T-DOX, is constructed, that carries appropriately low-density cilengitide, an alpha v beta 3 integrin-specific Arg-Gly-Asp (RGD)-mimetic cyclic peptide, via a membrane type 1-matrix metalloproteinase (MT1-MMP) cleavable peptide. After being administered systemically in a hypoperfused pancreatic cancer mouse model at a low dose of cilengitide, the proangiogenic activity of MC-T-DOX is specifically turned on in tumor vessels through cleavage by MT1-MMP on tumor endothelial cells to release cilengitide. This locally released cilengitide increases tumor blood perfusion, thereby improving the accumulation and distribution of MC-T-DOX in the tumor site. The loaded-DOX then displays enhanced penetration and increased cellular uptake upon heat-triggered release from MC-T-DOX in the tumor interstitium, contributing to the improved tumor therapy efficacy. Therefore, the strategy of combining the modulation of tumor vascular promotion with smart nanodrug delivery represents a promising approach to improving drug delivery and therapeutic efficacy in a wide range of hypoperfused tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据