Matrix Metalloproteinase Cleavable Nanoparticles for Tumor Microenvironment and Tumor Cell Dual-Targeting Drug Delivery

• DOI: 10.1021/acsami.7b11614
• Publication Date: 2017-11-03T12:25:38Z
• Authors: Zhenliang Sun; Ruihong Li; Ji Sun; You Peng; Linlin Xiao; Xingxing Zhang; Yixin Xu; Man Wang
• Keywords: 0301 basic medicine; Mice; 03 medical and health sciences; Drug Delivery Systems; Cell Line, Tumor; Tumor Microenvironment; Animals; Nanoparticles; Matrix Metalloproteinases; 3. Good health

Matrix metalloproteinases (MMPs), mostly abundant in the tumor extracellular matrix (ECM), cells, and vasculatures, are closely correlated with progression metastasis. In this case, making use of MMPs was supposed to achieve site-specific drug delivery a satisfactory treatment effect. Herein, we rationally developed novel microenvironment cell dual-targeting nanoparticle by integrating chemotherapeutic-loaded drug-loaded carrier versatile polypeptide-LinTT1-PVGLIG-TAT (LPT) which is composed multitargeting peptide-LinTT1 cell-penetrating peptide-TAT. The functionalized nanoparticles exhibited superior affinity A549 lung-cancer cells including angiogenesis tumor-associated macrophages (TAMs) our study. addition, cellular experiments demonstrated that ability TAT significantly shielded addition LinTT1 fourth lysine via an MMP cleavable linker PVGLIG could be recovered under catalysis MMPs. This design efficiently decrease toxicological risk normal tissues induced unselectivity TAT. finally effect investigation showed tumor-bearing mice treated LPT-modified achieved enhanced efficacy for inhibiting growth longest survival time as compared other groups. Collectively, study provides robust nanoplatform simultaneously target increasing cancer therapy.