フッ素化ゼオライト型イミダゾレートフレームワークナノシートによる局所水素ガス送達を用いたがん免疫療法の増強
To address the need for improved immune checkpoint blockade (ICB) efficacy, hepta-fluorinated zeolitic imidazolate framework nanosheets (F-ZIF) were engineered to carry high payloads of molecular hydrogen (H2) with acid-responsive, sustained release properties. Upon intratumoral delivery, F-ZIF/H2 released H2 and Zn2+ ions, inducing mitochondrial damage and apoptosis in tumor cells. A notable finding was that F-ZIF/H2 markedly elevated CD47 expression on tumor cells, increasing the accessibility and binding efficiency of anti-CD47 antibody. RNA-sequencing analysis revealed that anti-CD47 antibody both disrupts CD47-SIRPα signaling and activates antibody-dependent cellular phagocytosis via macrophage Fc receptors. In melanoma models, combining F-ZIF/H2 with anti-CD47 achieved tumor inhibition rates of 90% (small tumors, ~50 mm³) and 83% (large tumors, ~200 mm³). Further addition of anti-PD-L1 elicited systemic T cell immunity capable of suppressing both primary and distal tumors, demonstrating a gas-assisted immunotherapeutic strategy.
F-ZIF/H2 releases H2 and Zn2+ in the acidic tumor microenvironment, causing mitochondrial damage and apoptosis while upregulating CD47 on tumor cells. This enhances anti-CD47 antibody binding and activates macrophage antibody-dependent cellular phagocytosis via Fc receptor engagement, amplifying anti-tumor immune responses.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/40864154