TY - JOUR
T1 - Transformable peptide nanocarriers for expeditious drug release and effective cancer therapy via cancer-associated fibroblast activation
AU - Zhao, Yuliang
AU - Ji, Tianjiao
AU - Zhao, Ying
AU - Ding, Yanping
AU - Wang, Jing
AU - Zhao, Ruifang
AU - Lang, Jiayan
AU - Qin, Hao
AU - Liu, Xiaoman
AU - Shi, Jian
AU - Tao, Ning
AU - Qin, Zhihai
AU - Nie, Guangjun
N1 - Funding Information:
The authors thank Professor Ju Zhang from Nankai University for providing PF179T-CAF cell line. This work was supported by the grants from MOST 973 (2012CB934004, 2011CB933400, and 2013CB932701), the NSFC (21320102003, 31170962, 51203032, 21373067, 31300822), and the Key Research Program of the Chinese Academy of Sciences, Grant No. KGZD-EW-T06. G.N. acknowledges the support from National Distinguished Young Scientists grant (31325010).
Publisher Copyright:
© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
PY - 2016/1/18
Y1 - 2016/1/18
N2 - 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.
AB - 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.
KW - cancer-associated fibroblasts
KW - drug delivery
KW - fibroblast activation protein-α
KW - morphological transformation
KW - peptide assembly
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U2 - 10.1002/anie.201506262
DO - 10.1002/anie.201506262
M3 - Article
C2 - 26283097
AN - SCOPUS:84954404444
VL - 55
SP - 1050
EP - 1055
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 3
ER -