Gold nanoparticles decorated FOLFIRINOX loaded liposomes for synergistic therapy of pancreatic cancer

Abstract

Pancreatic cancer is predicted to be the second highest cause of cancer deaths by 2030, with a mortality rate of 98 % and a 5-year survival rate of only 4-8 %. FOLFIRINOX which consists of four main ingredients has shown superior efficacy in treating patients with pancreatic cancer compared to other agents and combinations. However, toxicities have prevented full-dose use of FOLFIRINOX. In this study, we present the design of a liposome nanosystem that enables the sequential release of a drug combination that is called FOLFIRINOX using lipid-based nanosystem synergistic chemo/photothermal therapy approaches. The co-eccentric liposome allowed us to locate the drug molecules in different locations giving us the flexibility to release them in a selected order. Core liposome (L2) has a melting temperature of 53.63 °C, it was decorated by gold nanoparticle (L2@AuNP) to bring photothermal responsiveness. The outer liposome structure had a lower melting temperature, which facilitated the sequential release process. The efficacy of photothermal therapy for nanosystem was calculated. The results indicate that coating L2@AuNP nanostructure with L1 liposomes improves efficacy by stabilizing gold nanoparticles. FOLFIRINOX components are encapsulated in a concentric liposome structure according to the order of administration into the body. The concentric liposome structure enables the sequential release of multiple drugs due to the varying phase transition temperatures of the liposomes. The cytotoxic effect of these formulations was evaluated on Panc-1 pancreatic cancer cells; the lowest cell viability was obtained in 4 Liposome(L) under 5 min NIR irradiation. Combination therapy has a higher therapeutic efficacy (70.45 %) when compared to chemotherapy and photothermal therapy used separately. The study's results show the potential of combination therapies to improve therapeutic outcomes, providing a promising path for future research and clinical application.

Keywords: Au NP; Chemotherapy; Hyperthermia; Liposome; Pancreatic cancer; Photothermal therapy.