Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer-Associated Fibroblast Activation.
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.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Tianjiao
T
Ji
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Ying
Y
Zhao
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Yanping
Y
Ding
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Jing
J
Wang
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Ruifang
R
Zhao
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Jiayan
J
Lang
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Hao
H
Qin
CAS Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, 15 Datun Road, Beijing, 100101, China.
Xiaoman
X
Liu
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Jian
J
Shi
CAS Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, 15 Datun Road, Beijing, 100101, China.
Ning
N
Tao
CAS Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, 15 Datun Road, Beijing, 100101, China.
Zhihai
Z
Qin
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.
Guangjun
G
Nie
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing, 100190, China. zhaoyl@nanoctr.cn.
Yuliang
Y
Zhao
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D010455:Peptides
cancer-associated fibroblasts; drug delivery; fibroblast activation protein-α; morphological transformation; peptide assembly