期刊
CHEMICAL ENGINEERING JOURNAL
卷 433, 期 -, 页码 -出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2021.133847
关键词
Tumor-associated macrophages; Metal-organic frameworks; Iron efflux; Cancer immunotherapy; Antitumor immune memory
资金
- National Basic Research Program of China [2020YFA0710700, 2018YFA0208900]
- National Natural Science Foundation of China [81974459, 82073796, 81627901, 81773653, 81803018]
- Program for HUST Academic Frontier Youth Team [2018QYTD01]
Resetting M2-like tumor-associated macrophages to an antitumor phenotype is a promising strategy in cancer immunotherapy. Iron-based metal-organic frameworks conjugated with a macrophage-targeting peptide were developed to load diclofenac, which efficiently targeted M2-like TAMs and decreased efflux, enabling improved macrophage repolarization. The repolarized TAMs effectively killed and phagocytosed tumor cells and remodeled the tumor immune microenvironment to generate long-term antitumor immune memory.
Resetting M2-like tumor-associated macrophages (TAMs) to antitumor M1 phenotype is a promising strategy in cancer immunotherapy. Although iron-based nanoparticles exhibit the potential of M2-to-M1 macrophage repolarization, the efficient M2-like TAM targeting and the subsequent intracellular iron retention remains a big challenge. Here, M2 macrophage-targeting peptide-conjugated iron-based metal-organic frameworks are developed to load diclofenac (Dic@M2pep-Fe-MOF) for enhanced cancer immunotherapy. Dic@M2pep-Fe-MOF efficiently targets M2-like TAMs and decreases the efflux by hepcidin/ferroportin signaling pathway, enabling enhanced intracellular accumulation for improved M2-to-M1 macrophage repolarization. Dic@M2pep-Fe-MOFrepolarized M2-like TAMs efficiently kill and phagocytose tumor cells, and importantly remodel tumor immune microenvironment to generate long-term antitumor immune memory, eliciting strong anticancer efficacy with tumor recurrence inhibition. Our results support Dic@M2pep-Fe-MOF as a potential drug for cancer immunotherapy.
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