Absorbable microspheres sustaining epirubicin and TLR7 agonist release for transarterial chemo-immuno-embolization in liver tumor.

Transarterial chemoembolization is a preferred medical intervention for unresectable advanced liver tumor patients. Its clinical efficacy is, nevertheless, undermined by poor control over drug release and immunosuppressed tumor microenvironment. In this work, we report on absorbable microspheres with excellent loading and controlled release of epirubicin and imiquimod, a toll-like receptor 7 agonist (EPI/IMQ@Asphere) for transarterial chemo-immuno-embolization (TACIE) in liver tumors. EPI/IMQ@Asphere while stable during storage steadily releases EPI in 4 weeks and IMQ in one week, continuously inducing immunogenic cell death and immune activation, respectively. Strikingly, one single injection of EPI/IMQ@Asphere into subcutaneous H22 murine liver tumor achieves complete regression in 5 out of 7 mice, all of which show complete resistance to tumor rechallenge, in line with robust and durable anti-cancer immune response. TACIE in orthotopic VX2 rabbit model reveals significant shrinkage of primary liver tumor and complete prevention of pulmonary metastasis, in which TACIE not only occludes tumor arteries and kills tumor cells but also amplifies tumoral CD8/CD4 T cell infiltration. Overall, TACIE based on EPI/IMQ@Asphere offers a highly appealing therapeutic strategy for advanced liver cancers.