Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 3, Pages 1050-1055Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201506262
Keywords
cancer-associated fibroblasts; drug delivery; fibroblast activation protein-alpha; morphological transformation; peptide assembly
Categories
Funding
- MOST 973 [2012CB934004, 2011CB933400, 2013CB932701]
- NSFC [21320102003, 31170962, 51203032, 21373067, 31300822]
- Chinese Academy of Sciences [KGZD-EW-T06]
- National Distinguished Young Scientists grant [31325010]
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A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein- (FAP-), a protease specifically expressed on the surface of cancer-associated fibroblasts. The CAP self-assembled into fiber-like nanostructures in solution, while the presence of hydrophobic chemotherapeutic drugs readily transformed the assemblies into drug-loaded spherical nanoparticles. The disassembly of these nanoparticles (CAP-NPs) upon FAP- cleavage resulted in rapid and efficient release of the encapsulated drugs specifically at tumor sites. This Transformers-like drug delivery strategy could allow them to disrupt the stromal barrier and enhance local drug accumulation. Therapeutic results suggested that drug-loaded CAP-NPs hold promising tumor specificity and therapeutic efficacy for various solid tumor models, confirming its potential utility and versatility in antitumor therapy.
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