叶酸
福克斯
结直肠癌
奥沙利铂
医学
氟尿嘧啶
药理学
癌症研究
毒性
内科学
转移
免疫系统
免疫疗法
癌症
化疗
免疫学
作者
Jianfeng Guo,Zhuo Yu,Manisit Das,Leaf Huang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2020-04-13
卷期号:14 (4): 5075-5089
被引量:170
标识
DOI:10.1021/acsnano.0c01676
摘要
FOLFOX, the combinational strategy of folinic acid (FnA), 5-fluorouracil (5-Fu), and oxaliplatin (OxP), has been used as standard treatment of colorectal cancer (CRC) for decades. Despite the improved survival, patients still suffer from drawbacks such as low efficacy, high toxicity, and long course of treatment. New strategies to address these issues are needed to further clinical benefits. In this study, a nanoprecipitate (C26H35N9O7Pt) was formed by the active form of OxP ([Pt(DACH)(H2O)2]2+) and FnA, which was formulated into an aminoethyl anisamide targeted PEGylated lipid nanoparticle within microemulsions using nanoprecipitation technique. The resultant formulation (namely Nano-Folox) significantly promoted the blood circulation and tumor accumulation of platinum drug and FnA in an orthotopic CRC mouse model. Emerging evidence indicates that OxP can not only provide anticancer cytotoxic effects but also induce immunogenic cell death (a type of apoptosis that primes anticancer immune responses). Consequently, Nano-Folox demonstrated favorable chemo-immunotherapeutic activities in orthotopic CRC mice. In addition, when compared to FOLFOX the significantly stronger chemo-immunotherapeutic responses were achieved by the combination of Nano-Folox and 5-Fu without showing toxicity. Moreover, the anti-PD-L1 monoclonal antibody enhanced Nano-Folox/5-Fu for decreased liver metastases in mice. These results indicate the potential of Nano-Folox-based combination strategy for the treatment of CRC.
科研通智能强力驱动
Strongly Powered by AbleSci AI