Two nanoformulations induce reactive oxygen species and immunogenetic cell death for synergistic chemo-immunotherapy eradicating colorectal cancer and hepatocellular carcinoma

• DOI: 10.1186/s12943-020-01297-0
• Publication Date: 2021-01-06T07:03:25Z
• Authors: Jianfeng Guo; Zhuo Yu; Dandan Sun; Yifang Zou; Yun Liu; Leaf Huang
• Keywords: FOLFOX; Folinic acid; Immunogenic cell death; Combination therapy

Abstract Background FOLFOX is a combinational regimen of folinic acid (FnA, FOL ), fluorouracil (5-Fu, F ) and oxaliplatin (OxP, OX has been long considered as the standard treatment colorectal cancer (CRC) hepatocellular carcinoma (HCC). Recent developments nano delivery systems have provided profound promise for improving anticancer efficacy alleviating side effects FOLFOX. Previously, nanoformulation (termed Nano-Folox) containing OxP derivative FnA was developed in our laboratory using nanoprecipitation technique. Nano-Folox induced OxP-mediated immunogenic cell death (ICD)-associated antitumor immunity, which significantly suppressed tumor growth orthotopic CRC mouse model when administrated combination with free 5-Fu. Methods A Nano-FdUMP) FdUMP (5-Fu active metabolite) newly technique used HCC therapies. Results Synergistic achieved models. It resulted mainly from fact that Nano-FdUMP mediated formation reactive oxygen species (ROS), promoted ICD elicited by Nano-Folox. In addition, Nano-Folox/Nano-FdUMP anti-PD-L1 antibody inhibited liver metastasis, leading to long-term survival mice. Conclusion This study provides proof concept two can result successful FOLFOX-associated Further optimization terms dosing timing will enhance clinical potential this strategy patients. Graphical abstract