Development of Cytolytic Iridium-Complexed Octaarginine Peptide Albumin Nanomedicine for Hepatocellular Carcinoma Treatment.

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.