Targeting Tumor-Associated Macrophages by MMP2-Sensitive Apoptotic Body-Mimicking Nanoparticles

• DOI: 10.1021/acsami.0c15983
• Publication Date: 2020-11-10T14:40:28Z
• Authors: Yin Liu; Jiao Wang; Jian Zhang; Sandra Marbach; Wei Xu; Lin Zhu
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Dasatinib; Antineoplastic Agents; Apoptosis; Phosphatidylserines; Polyethylene Glycols; 3. Good health; Mice; 03 medical and health sciences; RAW 264.7 Cells; Phagocytosis; Cell Line, Tumor; Larva; Neoplasms; Tumor-Associated Macrophages; Animals; Humans; Matrix Metalloproteinase 2; Nanoparticles; Female; Tissue Distribution; Zebrafish

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.