Abstract
OBJECTIVE: Hepatocellular carcinoma is one of the most challenging malignancies and has high incidence and mortality rates worldwide. Digital subtraction angiography (DSA)-guided hepatic arterial infusion of the standard chemotherapeutic agent oxaliplatin (OXA) has the advantages of both precision and efficacy, making it an important therapeutic strategy for advanced-stage liver cancer. However, patients receiving this treatment still face severe systemic toxicity and poor tolerability of oxaliplatin. METHODS: In this study, we compared oxaliplatin with novel albumin-formulated oncolytic peptide nanoparticles, Ir-cR8 (abbreviated as iPep), in the treatment of orthotopic liver cancer in a mouse model by intravenous injection and in a rabbit model via DSA-guided hepatic arterial infusion. RESULTS: The results showed that intravenous Ir-cR8-BSA-NPs had enhanced inhibitory effects to the growth of H22 ectopic liver tumors in mice and also with reduced toxicity in animals compared to OXA treatment. Specifically, Ir-cR8-BSA-NPs-treated mice showed approximately 92% tumor growth inhibition compared to approximately 88% for OXA. In the rabbit VX2 ectopic hepatocellular carcinoma model, Ir-cR8-BSA-NPs demonstrated significantly stronger inhibition (P<0.01) of tumor size compared to OXA, as assessed by PET/CT imaging, with SUV values decreasing from 5.15±0.46 to 2.52±0.57, compared to OXA-treated group, which decreased from 5.44±0.43 to 3.90±0.24. Furthermore, Ir-cR8- BSA-NPs significantly improved stability by albumin encapsulation and reduced hemolytic toxicity (P<0.001), resulting in improved therapeutic efficacy. CONCLUSION: This study demonstrated the combined advantages of a novel membrane-active oncolytic peptide nanomedicine and precise drug delivery enabled by arterial infusion technology for the interventional treatment of liver cancer.