MnFe_(2)O_(4)@HMD纳米酶的合成及体外抗小细胞肺癌作用  

Synthesis and in vitro anti-small cell lung cancer effects of MnFe_(2)O_(4)@HMD nanozyme

作　　者：何敬川 李婷婷 潘晓琴[1] 高明 阳洁 HE Jing-chuan;LI Ting-ting;PAN Xiao-qin;GAO Ming;YANG Jie(Dept of Pharmacology,School of Pharmacy,Guangxi Medical University,Nanning 530021,China;Dept of Pharmacy,Affiliated Tumor Hospital of Guangxi Medical University,Nanning 530021,China;Dept of Pharmacy,the Second Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637100,China;Life Sciences Institute,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,广西南宁530021 [2]广西医科大学附属肿瘤医院药学部,广西南宁530021 [3]川北医学院第二附属医院药剂科,四川南充637100 [4]广西医科大学生命科学研究院,广西南宁530021

出　　处：《中国药理学通报》2024年第11期2075-2082,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82160698,82374093);广西自然科学基金项目重点项目(No 2023GXNSFDA026026)。

摘　　要：目的制备MnFe_(2)O_(4)@HMD纳米酶,研究其体外抗小细胞肺癌活性。方法通过酯化反应及酰化反应合成HMD,通过共沉淀法合成MnFe_(2)O_(4),并在超声及磁力搅拌下合成MnFe_(2)O_(4)@HMD;通过FTIR、UV-vis、Zeta电位、XRD对MnFe_(2)O_(4)@HMD进行表征;TEM及DLS评估MnFe_(2)O_(4)@HMD的形态及粒径分布;MTT法及活/死细胞染色研究MnFe_(2)O_(4)@HMD对H1688细胞活力的影响;共聚焦显微镜观察H1688细胞对MnFe_(2)O_(4)@HMD的摄取情况;DCF-HA染色法及GSH试剂盒检测MnFe_(2)O_(4)@HMD对H1688细胞ROS及GSH水平的影响;Western blot检测MnFe_(2)O_(4)@HMD对H1688细胞中凋亡相关蛋白Bax及Bcl-2表达的影响。结果成功制备MnFe_(2)O_(4)@HMD纳米酶,其Zeta电位及粒径分别为-14.57±1.81 mV、27.1 nm;MnFe_(2)O_(4)@HMD对H1688细胞具有浓度依赖性杀伤作用;H1688细胞对MnFe_(2)O_(4)@HMD具有良好的摄取行为;MnFe_(2)O_(4)@HMD可呈浓度依赖性诱导H1688细胞ROS的产生及GSH的消耗,并上调H1688细胞促凋亡蛋白Bax、下调抗凋亡蛋白Bcl-2的表达。结论MnFe_(2)O_(4)@HMD对H1688细胞具有良好的杀伤作用,可导致ROS的升高及GSH的消耗,并诱导H1688细胞发生凋亡。Aim To synthesize MnFe_(2)O_(4)@HMD nanozyme and investigate its anti-small cell lung cancer activity.Methods HMD was synthesized by esterification and acylation reactions,MnFe_(2)O_(4) was synthesized by co-precipitation,and MnFe_(2)O_(4)@HMD was synthesized under ultrasound and magnetic stirring.MnFe_(2)O_(4)@HMD was characterized by FTIR,UV-vis,Zeta potential,and XRD.The morphology and particle size distribution of MnFe_(2)O_(4)@HMD were assessed by TEM and DLS.MTT assay and live/dead cell staining were used to evaluate the effect of MnFe_(2)O_(4)@HMD on the viability of H1688 cells.Confocal microscopy was used to observe the uptake of MnFe_(2)O_(4)@HMD by H1688 cells.DCF-HA staining and GSH kit were used to detect the effect of MnFe_(2)O_(4)@HMD on the levels of ROS and GSH in H1688 cells.Western blot was used to detect the effect of MnFe_(2)O_(4)@HMD on the expression of apoptosis-related proteins Bax and Bcl-2 in H1688 cells.Results MnFe_(2)O_(4)@HMD nanozymes were successfully synthesized,with zeta potential and particle size of-14.57±1.81 mV and 27.1 nm,respectively.MnFe_(2)O_(4)@HMD had a concentration-dependent toxicity effect on H1688 cells.H1688 cells showed a good uptake behavior of MnFe_(2)O_(4)@HMD.MnFe_(2)O_(4)@HMD could induce ROS production and GSH consumption in H1688 cells in a concentration-dependent manner,and up-regulated the expression of pro-apoptotic protein Bax and down-regulated anti-apoptotic protein Bcl-2 in H1688 cells.Conclusion MnFe_(2)O_(4)@HMD shows good killing effect on H1688 cells,which could lead to the elevation of ROS and the depletion of GSH,and induce apoptosis in H1688 cells.

关 键 词：MnFe_(2)O_(4) 纳米酶 小细胞肺癌 透明质酸 肿瘤靶向 凋亡 ROS 

分 类 号：R734.2[医药卫生—肿瘤]