Dual-targeted microspheres reshape the metabolic-immune microenvironment to reverse post-embolization dilemmas in hepatocellular carcinoma - PubMed
4 hours ago
- #hepatocellular carcinoma
- #immunotherapy
- #gas therapy
- Dual-targeted pH-responsive gelatin microspheres (ZnS@GMs) were developed to deliver hydrogen sulfide (H2S) and Zn2+ ions for addressing post-embolization challenges in hepatocellular carcinoma (HCC).
- ZnS@GMs inhibit tumor growth by suppressing the HIF-1α/VEGF axis and glycolytic metabolism, while promoting vascular normalization and immune activation.
- Mechanistically, H2S disrupts mitochondrial respiration to increase oxygen and destabilize HIF-1α, and Zn2+ inhibits hexokinase and lactate dehydrogenase to deplete ATP and biosynthetic intermediates.
- The microspheres induce immunogenic cell death, leading to dendritic cell maturation, cytotoxic T cell infiltration, macrophage repolarization, and enhanced efficacy of anti-PD-1 therapy.
- In a rabbit orthotopic liver tumor model, intra-arterial infusion of ZnS@GMs showed potent antitumor effects and effective embolic performance, offering a multifunctional platform to overcome TAE resistance in HCC.