期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 142, 期 29, 页码 12579-12584出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.0c05039
关键词
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资金
- National Cancer Institute [U01-CA198989]
- Department of Defense [PC170934P2]
- University of Chicago Medicine Comprehensive Cancer Center [NIH CCSG: P30 CA014599]
- Ludwig Institute for Metastasis Research
Nanoscale metal-organic frameworks (nMOFs) are excellent radiosensitizers for radiotherapy-radiodynamic therapy (RT-RDT). Herein, we report surface modification of a Hf-DBP nMOF for the co-delivery of a hydrophobic small-molecule toll-like receptor 7 agonist, imiquimod (IMD), and a hydrophilic macromolecule, anti-CD47 antibody (alpha CD47), for macrophage modulation and reversal of immunosuppression in tumors. IMD repolarizes immunosuppressive M2 macrophages to immunostimulatory M1 macrophages, while alpha CD47 blocks CD47 tumor cell surface marker to promote phagocytosis. Upon X-ray irradiation, IMD@Hf-DBP/alpha CD47 effectively modulates the immunosuppressive tumor microenvironment and activates innate immunity to orchestrate adaptive immunity when synergized with an anti-PD-L1 immune checkpoint inhibitor, leading to complete eradication of both primary and distant tumors on a bilateral colorectal tumor model. nMOFs thus provide a unique platform to co-deliver multiple immunoadjuvants for macrophage therapy to induce systematic immune responses and superb antitumor efficacy.
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