PUBLICATION
Targeting Tumor-Associated Macrophages by MMP2-Sensitive Apoptotic Body-Mimicking Nanoparticles
- Authors
- Liu, Y., Wang, J., Zhang, J., Marbach, S., Xu, W., Zhu, L.
- ID
- ZDB-PUB-201120-81
- Date
- 2020
- Source
- ACS applied materials & interfaces 12(47): 52402-52414 (Journal)
- Registered Authors
- Keywords
- apoptotic body, drug delivery, matrix metalloproteinase 2, nanoparticles, phosphatidylserine, tumor-associated macrophages
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use
- Apoptosis*/drug effects
- Cell Line, Tumor
- Dasatinib/chemistry
- Dasatinib/pharmacology
- Dasatinib/therapeutic use
- Female
- Humans
- Larva/metabolism
- Matrix Metalloproteinase 2/metabolism*
- Mice
- Mice, Inbred BALB C
- Nanoparticles/chemistry*
- Nanoparticles/metabolism
- Nanoparticles/toxicity
- Neoplasms/drug therapy
- Neoplasms/pathology
- Phagocytosis
- Phosphatidylserines/chemistry
- Polyethylene Glycols/chemistry
- RAW 264.7 Cells
- Tissue Distribution
- Tumor-Associated Macrophages/cytology
- Tumor-Associated Macrophages/drug effects
- Tumor-Associated Macrophages/metabolism*
- Zebrafish/growth & development
- Zebrafish/metabolism
- PubMed
- 33169982 Full text @ ACS Appl. Mater. Interfaces
Citation
Liu, Y., Wang, J., Zhang, J., Marbach, S., Xu, W., Zhu, L. (2020) Targeting Tumor-Associated Macrophages by MMP2-Sensitive Apoptotic Body-Mimicking Nanoparticles. ACS applied materials & interfaces. 12(47):52402-52414.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping