Open AccessTargeting Tumor-Associated Macrophages by MMP2-Sensitive Apoptotic Body-Mimicking Nanoparticles
Author(s) -
Yin Liu,
Jiao Wang,
Jian Zhang,
Sandra Marbach,
Wei Xu,
Lin Zhu
Publication year - 2020
Publication title -
acs applied materials and interfaces
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.535
H-Index - 228
eISSN - 1944-8252
pISSN - 1944-8244
DOI - 10.1021/acsami.0c15983
Subject(s) - mmp2 , tumor microenvironment , phagocytosis , cancer research , apoptosis , drug delivery , materials science , matrix metalloproteinase , macrophage , nanoparticle , microbiology and biotechnology , nanotechnology , cancer , chemistry , tumor cells , biology , in vitro , metastasis , biochemistry , genetics
Tumor-associated macrophages (TAMs), a major player in the tumor microenvironment, were recently recognized as a potential therapeutic target. To date, very few anticancer drugs or drug-delivery systems were designed to target the TAMs. Inspired by the "eat me" signal, phosphatidylserine (PS), mediated phagocytic clearance of apoptotic bodies, in this study, the matrix metalloproteinase 2 (MMP2)-sensitive PS-modified nanoparticles were developed. In the design, the PS is externalized to the nanoparticles' surface only when the nanoparticles reach the MMP2-overexpressing tumor site, allowing for the TAM-specific phagocytosis. The nanoparticles' excellent macrophage/TAM selectivity was observed in various biological models, including various cell lines, coculture cells, coculture cell spheroids, zebrafish, and tumor-bearing mice. The nanoparticles' TAM specificity remarkably enhanced the TAM depletion capability of the loaded model drug, dasatinib, resulting in the improved anticancer activity. The MMP2-sensitive apoptotic body-mimicking nanoparticles might be a promising delivery tool for TAM-centered cancer diagnoses and treatments.