MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy
| Autor: | Nianxiu Duan, Shiyan Guo, Chengyuan Peng, Sha Song, Yiwei Yang, Yong Gan, Xinxin Zhang, Di Nie, Feng Wang, Yuxi Wang, Junjun Li, Miaorong Yu, Yan Wei, Chunliu Zhu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
vascular promotion
General Chemical Engineering pancreatic cancer General Physics and Astronomy Medicine (miscellaneous) Cilengitide 02 engineering and technology Matrix metalloproteinase 010402 general chemistry 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) chemistry.chemical_compound Pancreatic cancer Medicine General Materials Science Doxorubicin lcsh:Science Metalloproteinase Liposome Full Paper business.industry smart liposomes General Engineering Full Papers 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences chemistry membrane type 1‐matrix metalloproteinase‐activated cilengitide Drug delivery Cancer research lcsh:Q 0210 nano-technology business Perfusion medicine.drug |
| Zdroj: | Advanced Science, Vol 7, Iss 17, Pp n/a-n/a (2020) Advanced Science |
| ISSN: | 2198-3844 |
| DOI: | 10.1002/advs.201902746 |
| Popis: | 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 αvβ3 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. Low‐density membrane type 1‐matrix metalloproteinase (MT1‐MMP)‐activated cilengitide (MC) is modified onto thermosensitive liposomes loaded with doxorubicin (DOX), yielding MC‐T‐DOX. MC‐T‐DOX is activated by MT1‐MMP on tumor endothelial cells to release cilengitide, which then improves tumor blood perfusion, thereby enhancing intratumoral delivery of MC‐T‐DOX. Subsequently, in the interstitium, heat‐triggered DOX release from MC‐T‐DOX facilitates its bioavailability, thereby exerting improved antitumor efficacy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text