Targeted Chemoimmunotherapy for Hepatocellular Carcinoma: Dual-Stimulus Responsive Nanocarrier for Enhanced Antitumor Response

Abstract

Abstract Hepatocellular carcinoma (HCC) remains a global health challenge and accounts for ~ 90% of liver cancers. Immunotherapy is demonstrating potent potential for HCC treatment. However, the therapeutic efficacy has been impeded by poor immunogenicity and immunosuppressive tumor microenvironment. Herein, we developed a dual-stimulus responsive nanocarrier (PN@GPB-PEG NPs) to co-deliver chemotherapeutic agent paclitaxel (PTX) and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG919 for HCC chemoimmunotherapy. The resulting nanoparticles demonstrated tumor-specific accumulation and efficient cellular uptake in HCC cells. Furthermore, rapid cargo release could be observed as reactive oxygen species (ROS) triggered disassembly within tumor cells. PTX triggered immunogenic cell death (ICD) to provoke antitumor immune responses meanwhile NLG919 mediated IDO inhibition relieved immunosuppression in tumor microenvironment. As a result, the dual-stimulus responsive nanoparticles efficiently boosted the synergistic antitumor effects and inhibited postoperative tumor recurrence in a mouse HCC model. Hence, the nanoparticles provide a promising strategy for HCC chemoimmunotherapy.