期刊
ADVANCED MATERIALS
卷 34, 期 14, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202200389
关键词
cancer immunotherapy; hollow mesoporous Prussian blue; hydroxychloroquine; hybrid membranes; tumor-associated macrophages
类别
资金
- National Natural Science Foundation of China [81972893]
- Excellent Youth Science Foundation of Henan province [212300410071]
- Training program for young key teachers in Henan Province (China) [2020GGJS019]
- National University of Singapore [NUHSRO/2020/133/Startup/08]
- NUS School of Medicine Nanomedicine Translational Research Programme [NUHSRO/2021/034/TRP/09/Nanomedicine]
This study successfully addresses the limitations of tumor-associated macrophages and hypoxia conditions in cancer immunotherapy by developing a hollow mesoporous Prussian blue nanosystem with mannose decoration and hydroxychloroquine adsorption. In vivo experiments demonstrate that this system effectively inhibits tumor growth, induces macrophage polarization, promotes cytotoxic T lymphocytes infiltration, and alleviates hypoxia microenvironment.
Both tumor-associated macrophages (TAMs) and hypoxia condition severely restrict the antitumor potency during cancer immunotherapy. It is essential to overcome the two issues for improving therapeutic efficacy. In this study, a hollow mesoporous Prussian blue (HMPB) nanosystem with mannose decoration and hydroxychloroquine (HCQ) adsorption is built, to form Man-HMPB/HCQ. It can facilitate cellular internalization via mannose-receptor mediated endocytosis and induce TAM polarization via iron ion/HCQ release with HMPB degradation. The hybrid macrophage and thylakoid (TK) membrane is camouflaged on the Man-HMPB/HCQ surface, denoted as TK-M@Man-HMPB/HCQ, to reduce in vivo reticuloendothelial system uptake, enhance tumor accumulation, and mitigate hypoxia. The in vivo results indicate that TK-M@Man-HMPB/HCQ notably inhibits tumor growth, induces TAM polarization, facilitates cytotoxic T lymphocytes infiltration, and alleviates hypoxia microenvironment. The rational design may provide a new pathway to modulate the tumor microenvironment for promoting cancer immunotherapy effects.
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