Synergistic nanoparticle dyad improving tumor immunogenicity and reshaping tolerogenic dendritic cells in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains a global health challenge with limited treatment efficacy despite advances in immune checkpoint blockade (ICB). The low immunogenicity of HCC tumors and impaired dendritic cell (DC) function contribute to suboptimal therapeutic outcomes. To address these limitations, we developed a synergistic nanoparticle dyad combining tumoricidal and immunomodulatory components. Specifically, an anti-GPC3-antibody-conjugated, emodin-loaded spiky mesoporous silica nanoparticle (E-SMSNα) selectively targets HCC cells to induce immunogenic cell death, while a matured DC-membrane-camouflaged, c-di-AMP-loaded nanoparticle (A-MSNm) reprograms dysfunctional DCs, bridging innate and adaptive immunity. This combinatorial approach synergistically promotes antitumor immunity, significantly suppressing primary tumor growth and inducing durable protection against tumor rechallenge. Moreover, it shows strong synergy with PD-1 checkpoint blockade, positioning it as a promising strategy for HCC immunotherapy.