Improved Hepatocellular Carcinoma Targeted Combination Immunotherapy Using a Nanocarrier: Monitoring Tumor Response via Functional MRI

Motivation: To enhance the efficacy of hepatocellular carcinoma immunotherapy using a nanocarrier and to explore IVIM-MRI for monitoring the tumor immune microenvironment. Goal(s): To synthesize iRGD-targeted liposomes to enhance the treatment efficacy of hepatocellular carcinoma and to develop effective biomarkers for the tumor microenvironment. Approach: We synthesized iRGD-modified liposomal co-encapsulating Lenvatinib and BMS-202. IVIM-MRI was performed before and at 6 and 12 days after treatments, followed by pathological examination after the final scan. Results: iRGD-lip@Len/BMS-202 promotes tumor vascular normalization and effectively activates an anti-tumor immune response. Importantly, the derived parameters D* and f are significantly correlated with tumor vascular normalization and immune activation. Impact: The iRGD-targeted dual-drug liposomal nanoparticles exhibited potent synergistic anti-tumor effects. Additionally, IVIM-MRI facilitated the monitoring of changes in the tumor microenvironment, with the D* and f parameters serving as valuable indicators for evaluating tumor vascular network and immune microenvironment modulation.