1.Experimental study on the therapeutic effect of brucine nanoparticles on hepatocellular carcinoma
Jianmin QIN ; Zhongqiu SA ; Xiajun XU ; Lin YANG ; Xia SHENG ; Min ZHANG ; Qi LI ; Peihao YIN ; Kepan GAO ; Qinghua CHEN
Chinese Journal of Hepatobiliary Surgery 2011;17(12):1005-1008
Objective To observe the therapeutic effect of brucine nanoparticles on hepatocellular carcinoma.Methods Brucine nanoparticles with block copolymer of carboxylation polyethylene glycol and polylactic acid were manufactured by ultraphonic emulsification.The effect brucine nanoparticles on growth of SMMC-7721 cell line was observed in vitro.The protein and mRNA levels of Fas were measured with Western blotting and FQ-PCR respectively after the brucine nanoparticles were added into cell culture fluid for 72 hours.Results The mean diameter,the carried drug rate and the entrapment rate of brucine nanopaticles was 146±96 nm,4.2% and 67%,respectively.The growth inhibition of liver cancer cells was enhanced significantly with the increasing drug dose.The IC50 of growth inhibition of 5-FU,brucine and brucine nanoparticles was 16.7 μg/ml,90.3 μg/ml and 164.9 μtg/ml,respectively.There was significant difference among them (P<0.05).The protein and mRNA expression of Fas in brucine nanoparticles treated SMMC-7721 cells increased significantly compared with that in blank control group(P<0.05).Conclusion Brucine nanoparticles may potentially be a novel therapeutic drug for hepatocellular carcinoma.
2.Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine.
Xing DUAN ; Yi ZHANG ; Mengran GUO ; Na FAN ; Kepan CHEN ; Shugang QIN ; Wen XIAO ; Qian ZHENG ; Hai HUANG ; Xiawei WEI ; Yuquan WEI ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2023;13(3):942-954
The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.