5-fluorouracil nanoparticles inhibit hepatocellular carcinoma via activation of the p53 pathway in the orthotopic transplant mouse model5 -氟尿嘧啶纳米粒子通过激活抑制肝细胞癌p53通路的原位移植小鼠模型.pdfVIP

5-Fluorouracil Nanoparticles Inhibit Hepatocellular Carcinoma via Activation of the p53 Pathway in the Orthotopic Transplant Mouse Model 1,2 2 3 2 1 4 3 Mingrong Cheng , Bing He *, Tao Wan *, Weiping Zhu , Jiang Han , Bingbing Zha , Houxiang Chen , 3 5 1 2 2 Fengxiao Yang , Qing Li , Wei Wang , Hongzhi Xu , Tao Ye 1 Department of General Surgery, Zhoupu Hospital of Shanghai Pudong New Area, Shanghai, China, 2 Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China, 3 Biomedical Materials and Engineering Center, Wuhan University of Technology, Wuhan, China, 4 Department of Endocrine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China, 5 Department of General Medicine, Pujiang Hospital of Shanghai Fifth People’s Hospital, Shanghai, China Abstract Biodegradable polymer nanoparticle drug delivery systems provide targeted drug delivery, improved pharmacokinetic and biodistribution, enhanced drug stability and fewer side effects. These drug delivery systems are widely used for delivering cytotoxic agents. In the present study, we synthesized GC/5-FU nanoparticles by combining galactosylated chitosan (GC) material with 5-FU, and tested its effect on liver cancer in vitro and in vivo. The in vitro anti-cancer effects of this sustained release system were both dose- and time-dependent, and demonstrated higher cytotoxicity against hepatic cancer cells than against other cell types. The distribution of GC/5-FU in vivo revealed the greatest accumulation in hepatic cancer tissues. GC/5-FU significantly inhibited tumor growth in an orthotropic liver cancer mouse model, resulting in a significant