作者：

Nan Jiang^1#, Zifan Pei^2#, Fei Gong^2#, Weihao Yang¹, Jiachen Xu³, Jie Cao², Xiaoxiao Pan², Bin Yu¹, Jian Shen¹, Zhi Li¹, Binyan Zhong⁴, Caifang Ni¹*, and Liang Cheng²*

单位：

¹Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China

²Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon Based Functional Materials & Devices, Soochow University, Suzhou 215123, China

³Department of Vascular Surgery and Interventional Radiology, The Fourth Affiliated Hospital of Soochow University, Dushu Lake Hospital Affiliated to Soochow University, Suzhou 215125, China

⁴Department of Interventional Radiology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310052, China

摘要：

Transarterial embolization (TAE) efficacy in hepatocellular carcinoma (HCC) is limited by post-embolization hypoxia-driven angiogenesis and metabolic reprogramming. To address this, we develop pH-responsive gelatin microspheres (GMs) encapsulating zinc sulfide (ZnS) nanoparticles (ZnS-encapsulated gelatin microspheres [ZnS@GMs]) for the dual delivery of hydrogen sulfide (H₂S) gas and Zn²⁺ ions. ZnS@GMs inhibit tumor growth through suppression of the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) axis and glycolytic metabolism, alongside promoting vascular normalization and immune activation. Mechanistically, H₂S disrupts mitochondrial respiration, increasing oxygen levels and destabilizing HIF-1α, whereas Zn²⁺ inhibits hexokinase and lactate dehydrogenase, depleting ATP and biosynthetic intermediates. Furthermore, ZnS@GMs induce immunogenic cell death, which triggers dendritic cell maturation, cytotoxic T cell infiltration, and macrophage repolarization, thereby enhancing the efficacy of anti-PD-1 therapy. In a rabbit orthotopic liver tumor model, intra-arterial infusion of ZnS@GMs confirms potent antitumor effects and effective embolic performance. This work establishes ZnS@GMs as a multifunctional platform to overcome TAE resistance in HCC.

影响因子：

10.6

分区情况：

一区

链接：

https://doi.org/10.1016/j.xcrm.2026.102748