Biomimetic selenium nanomedicine with homologous targeting enhances hepatocellular carcinoma therapy

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited effective therapeutic options. While trace elements like selenium (Se)-based nanoparticles (SeNPs) show promising anti-tumor effects, their clinical application is greatly hindered by poor targeting efficiency. Here, we engineered a biomimetic Se nanomedicine, CCEVSe, by encapsulating SeNPs within tumor cell-derived extracellular vesicles (CCEVs). Utilizing the inherent homotypic targeting and immune-evasion properties of CCEVs, CCEVSe selectively targets and is effectively internalized by tumor cells of the same origin. <i>In vitro</i> studies confirmed that CCEVSe exhibits superior cytotoxicity by amplifying intracellular reactive oxygen species and inhibiting key malignant behaviors, including proliferation, stemness, and metastasis. <i>In vivo</i> experiments in an HCC xenograft mouse model revealed that CCEVSe achieved superior tumor-specific accumulation, with Se concentrations in tumors approximately four times higher than free SeNPs after one injection. This enhanced targeting led to significant therapeutic efficacy, with CCEVSe achieving up to 87 % tumor growth suppression while exhibiting excellent safety with no observable systemic toxicity. In summary, our study provides a new paradigm for the cell-selective delivery of therapeutic nanomaterials through biomimetic modification, offering a promising strategy for precise HCC therapy.