MT1-MMP-Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy.
Adv Sci (Weinh)
; 7(17): 1902746, 2020 Sep.
Article
in En
| MEDLINE
| ID: mdl-32995113
ABSTRACT
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 αvß3 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2020
Document type:
Article