Drug-Eluting Shear-Thinning Hydrogel for the Delivery of Chemo- and Immunotherapeutic Agents for the Treatment of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a malignant and deadly form of liver cancer with limited treatment options. Transcatheter arterial chemoembolization, a procedure that delivers embolic and chemotherapeutic agents through blood vessels, is a promising cancer treatment strategy. However, it still faces limitations, such as inefficient agent delivery and the inability to address tumor-induced immunosuppression. Here, a drug-eluting shear-thinning hydrogel (DESTH) loaded with chemotherapeutic and immunotherapeutic agents in nanocomposite hydrogels composed of gelatin and nanoclays is presented as a therapeutic strategy for a catheter-based endovascular anticancer approach. DESTH is manually deliverable using a conventional needle and catheter. In addition, drug release studies show a sustained and pH-dependent co-delivery of the chemotherapy doxorubicin (acidic pH) and the immune-checkpoint inhibitor aPD-1 (neutral pH). In a mouse liver tumor model, the DESTH-based chemo/immunotherapy combination has the highest survival rate and smallest residual tumor size. Finally, immunofluorescence analysis confirms that DESTH application enhances cell death and increases intratumoral infiltration of cytotoxic T-cells. In conclusion, the results show that DESTH, which enables efficient ischemic tumor cell death and effective co-delivery of chemo- and immunotherapeutic agents, may have the potential to be an effective therapeutic modality in the treatment of HCC.