Due to the immunosuppressive tumor microenvironment (TME) and the low immunogenicity of tumor antigens, cancer vaccines face limitations. Immunogenic cell death (ICD) triggered by mitochondrial dysfunction is a promising strategy to enhance tumor antigen release and immune activation. However, actively amplifying mitochondrial damage-induced ICD remains challenging. In this study, we developed a vaccine in which liquid metal nanoparticles (LMPs) target tumor cells,Self-assembly and aggregation occur on the cell surface to achieve efficient uptake, intracellular fusion to prolong retention time, and the release of Ga³⁺ ions through an iron substitution pathway to induce mitochondrial damage, thereby triggering ICD. In combination with irreversible electroporation (IRE), this approach mediates sustained tumor-specific immunotherapy. Specifically, LMPs target integrin αvβ6 on tumor cells, initiating self-assembly and aggregation to achieve efficient cellular internalization. In the acidic lysosomal environment, LMPs undergo fusion and partially escape into the cytoplasm,This enables the long-term retention and sustained release of Ga³⁺ ions within cells. The released Ga³⁺ disrupts mitochondrial structure and inhibits electron transport through iron substitution, leading to significant mitochondrial damage. The synergistic effect of IRE and LMPs can increase the release of mitochondrial damage-associated DAMPs and tumor antigens, driving robust ICD and long-term systemic anti-tumor immunity. This dual-modal strategy provides a blueprint for nanomaterial-driven ICD amplification in cancer immunotherapy.

Original link

Liquid Metal Nanoparticles-Mediated Mitochondrial Damage Enhances Immunogenic Cell Death for Cancer Vaccine Therapy

Pub Date : 2026-01-05

DOI: 10.1002/adma.202520580

Yuxia Qi,  Zhongyang Yu,  Jie Zhang,  Chi Zhang,  Xiaoshuai Wang,  Fan Yang,  Yunlong Bai,  Jun‐Xiao Yuan,  Minghui Guo,  Dawei Wang,  Kaiwen Hu,  Tian Zhou,  Lei Wang,  Wei Rao