Natashya Falcone1, Menekse Ermis1, Ankit Gangrade1, Auveen Choroomi1, Patric Young1, Tess G. Mathes1, Mahsa Monirizad1, Fatemeh Zehtabi1, Marvin Mecwan1, Marco Rodriguez1, Yangzhi Zhu1, Youngjoo Byun2, Ali Khademhosseini1, Natan Roberto de Barros1, Han-Jun Kim1,3,4
1Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90024 USA
2Department of Pathophysiology and Preclinical Science College of Pharmacy, Korea University, 30019 Sejong, Republic of Korea
3Department of Pathophysiology and Preclinical Science College of Pharmacy, Korea University, 30019 Sejong, Republic of Korea
4Vellore Institute of Technology (VIT), Vellore, 632014 India
CORRESPONDING AUTHORS : Ali Khademhosseini, Natan Roberto de Barros, Han-Jun Kim
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.