Author:
Guo Jianfeng,Yu Zhuo,Sun Dandan,Zou Yifang,Liu Yun,Huang Leaf
Abstract
Abstract
Background
FOLFOX is a combinational regimen of folinic acid (FnA, FOL), fluorouracil (5-Fu, F) and oxaliplatin (OxP, OX), and has been long considered as the standard treatment of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Recent developments of nano delivery systems have provided profound promise for improving anticancer efficacy and alleviating side effects of FOLFOX. Previously, a nanoformulation (termed Nano-Folox) containing OxP derivative and 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 in the orthotopic CRC mouse model when administrated in combination with free 5-Fu.
Methods
A nanoformulation (termed Nano-FdUMP) containing FdUMP (5-Fu active metabolite) was newly developed using nanoprecipitation technique and used in combination with Nano-Folox for CRC and HCC therapies.
Results
Synergistic efficacy was achieved in orthotopic CRC and HCC mouse models. It resulted mainly from the fact that Nano-FdUMP mediated the formation of reactive oxygen species (ROS), which promoted the efficacy of ICD elicited by Nano-Folox. In addition, combination of Nano-Folox/Nano-FdUMP and anti-PD-L1 antibody significantly inhibited CRC liver metastasis, leading to long-term survival in mice.
Conclusion
This study provides proof of concept that combination of two nano delivery systems can result in successful FOLFOX-associated CRC and HCC therapies. Further optimization in terms of dosing and timing will enhance clinical potential of this combination strategy for patients.
Graphical abstract
Funder
National Institutes of Health
Health Commission of Jilin Province
Talents Cultivation Program of Jilin University
Fundamental Research Funds for the Central Universities
National Natural Science Foundation of China
China Scholarship Council
Chenguang Program from Shanghai Education Development Foundation and Shanghai Municipal Education Commission
Shanghai Rising-Star Program
Training Plan of Outstanding Young Medical Talents from Shanghai Municipal Health Bureau
Talent Youth Supporting Project from Chinese Medicine Association
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Medicine
Cited by
69 articles.
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