Local Delivery of Molecular Hydrogen by Fluorinated Zeolitic Imidazole Framework Nanosheets Boosts Cancer Immunotherapy
Date
2025
Authors
Liu, X.
Wang, W.
Wu, T.
Li, J.
Gong, Y.
Luo, D.
Guo, X.
Deng, M.
Yang, Y.
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Journal article
Citation
ACS applied materials & interfaces, 2025; 17(36):50548-50559
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Xiang Liu, Weidong Wang, Tianze Wu, Jianing Li, Yimin Gong, Dan Luo, Xianling Guo, Mingli Deng, and Yannan Yang
Conference Name
Abstract
Identifying strategies to improve the efficacy of the immune checkpoint blockade (ICB) remains a major clinical need. Based on the high tissue penetration capability of hydrogen molecules (H₂) and their immunomodulatory effects, this work proposes a local gas delivery strategy targeting the tumor microenvironment for high-efficacy hydrogen immunotherapy. We synthesized hepta-fluorinated zeolitic imidazolate frameworks nanosheet (F₇-ZIF) with high H₂ payload, sustained acid-responsive gas release property, and biodegradation. H₂-loaded F₇-ZIF (F₇-ZIF/H₂) effectively released H₂ and Zn²⁺ to induce significant mitochondrial damage and cell apoptosis. More importantly, F₇-ZIF/H₂ considerably upregulated the expression of CD47 (“do not eat me” signal) on tumor cells, which increases target accessibility for anti-CD47 antibody, thereby enhancing their binding efficiency. RNA-seq suggests that the CD47 antibody not only blocks the “do not eat me” signal (mediated by CD47-SIRPα interactions) but also engages Fc receptors on macrophages through its Fc region to trigger antibody-dependent cellular phagocytosis. In melanoma tumor models with small (∼50 mm³) and large sized established tumors (∼200 mm³), the combination of F₇-ZIF/H₂ and anti-CD47 reaches 90% and 83% of tumor inhibition rate, respectively, compared to free anti-CD47. When further combined with anti-PD-L1, the therapeutic system triggers systemic T cell immunity that rejects the progression of both primary and distal tumors. This work provides insights into gas-assisted cancer immunotherapy.
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© 2025 American Chemical Society