Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer-Associated Fibroblast Activation

• Published in: Angewandte Chemie International Edition 2016-01, Vol.55 (3), p.1050-1055
• Main Authors: Ji, Tianjiao, Zhao, Ying, Ding, Yanping, Wang, Jing, Zhao, Ruifang, Lang, Jiayan, Qin, Hao, Liu, Xiaoman, Shi, Jian, Tao, Ning, Qin, Zhihai, Nie, Guangjun, Zhao, Yuliang
• Format: Article
• Language: English
• Subjects: Accumulation; Animals; Antineoplastic Agents - administration & dosage; Assemblies; Cancer; Cancer therapies; cancer-associated fibroblasts; Cell Line, Tumor; Cleavage; Communication; Communications; Dismantling; Drug Carriers; Drug delivery; Drug delivery systems; Drugs; Effectiveness; Encapsulation; Fibroblast activation protein; fibroblast activation protein-α; Fibroblasts; Fibroblasts - metabolism; Hydrophobicity; Mice; Microscopy, Electron, Transmission; morphological transformation; Nanoparticles; Nanostructure; Neoplasms - drug therapy; Neoplasms - pathology; peptide assembly; Peptides - administration & dosage; Protease; Proteinase; Therapy; Transformers; Versatility; Xenograft Model Antitumor Assays
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201506262

A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein‐α (FAP‐α), 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‐α 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. A cleavable amphiphilic peptide (CAP) nanocarrier transforms from self‐assembled nanofibers to spherical nanoparticles (NPs) by loading hydrophobic drugs, and cleavage by the tumor‐specific protease, FAP‐α, resulted in specific and efficient release of the encapsulated drugs at tumor sites. This Transformers‐like drug nanocarrier could disrupt the stromal barrier, and enhance local drug accumulation.