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

作者：Chang Liu, Xiejun Zhao, Hui Song, Yiwen Yuan, Jia Ma, Yingtong Dong, Tianzhao Xu, Xiaojiao Li, X LIU · 发表于：Materials Today Bio · 年份：2026 · DOI：10.1016/j.mtbio.2026.103488 · 研究领域：Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers、Nanoplatforms for cancer theranostics

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.