叶酸修饰埃洛石纳米管负载姜黄素对乳腺癌细胞及移植瘤的放射增敏作用  

Radiosensitization of breast cancer cells and transplanted tumors by folate-modified halloysite nanotubes loaded with curcumin

作　　者：王寒剑 韩栋梁 危文祥 田卫群[1] WANG Hanjian;HAN Dongliang;WEI Wenxiang;TIAN Weiqun(Department of Biomedical Engineering,Wuhan University Taikang Medical School(School of Basic Medical Sciences),Hubei Wuhan 430071,China;Department of Oncology,General Hospital of Central Theater Command,Hubei Wuhan 430070,China)

机构地区：[1]武汉大学泰康医学院(基础医学院)生物医学工程系,湖北武汉430071 [2]中部战区总医院肿瘤科,湖北武汉430070

出　　处：《现代肿瘤医学》2023年第13期2379-2384,共6页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:81871493)。

摘　　要：目的:探究叶酸修饰埃洛石纳米管负载姜黄素(HNTs-PEG-FA/Cur)对乳腺癌MCF-7细胞及4T1荷瘤鼠的靶向放射增敏作用。方法:用化学改性和物理吸附的方法合成纳米放疗增敏药物HNTs-PEG-FA/Cur,采用透射电子显微镜、傅里叶红外光谱仪和X射线光电子能谱仪进行形貌和化学组分表征,MTT法检测不同浓度纳米药物对人乳腺癌MCF-7细胞活性的影响,流式细胞术、活/死细胞荧光染色和克隆形成实验评估HNTs-PEG-FA/Cur联合放疗对MCF-7细胞的促凋亡作用和放射增敏作用。最后,通过建立乳腺癌4T1细胞小鼠移植瘤模型,评估联合治疗对小鼠肿瘤体积生长的抑制效果。结果:成功将姜黄素负载于叶酸修饰的HNTs管腔内。所制备的HNTs-PEG-FA/Cur在等效姜黄素浓度为5μmol/L时对MCF-7细胞无明显毒性,并能有效增强X射线诱导的细胞凋亡和杀伤作用(增敏比为1.25)。体内抑瘤实验结果显示HNTs-PEG-FA/Cur联合放疗对小鼠肿瘤生长抑制率(56.75%)>单独射线组(24.16%)>单独药物组(6.67%)。结论:HNTs-PEG-FA作为姜黄素的新型纳米药物载体,能有效提高姜黄素生物利用度并且对乳腺癌具有靶向放射增敏潜力。Objective:To investigate the radiosensitizing effect of folate-modified halloysite nanotubes loaded with curcumin(HNTs-PEG-FA/Cur)on breast cancer cells MCF-7 and 4T1 transplanted tumors.Methods:The folate receptor-targeted nanomedicine HNTs-PEG-FA/Cur was prepared by chemical modification and physical adsorption,and characterized by TEM,FT-IR and XPS.The cytotoxicity of the nanodrug was detected by MTT assay,and the proapoptotic effect and in vitro radiosensitization of HNTs-PEG-FA/Cur combined with radiotherapy on MCF-7 cells were evaluated by flow cytometry,cell live/dead staining assay and cell clone formation assay.The volumetric growth inhibition of transplanted tumors was further validated by establishing 4T1 cell load-bearing mouse model.Results:HNTs were successfully modified and grafted with folic acid molecules,and curcumin was loaded into the lumen.Cytotoxicity assay showed no significant effect of HNTs-PEG-FA/Cur on cell proliferation at an equivalent curcumin concentration of 5μmol/L.Cell live/dead staining and flow cytometry results showed that combined 6 Gy of X-ray significantly promoted apoptosis.The results of clone formation assay showed a radiosensitization ratio of 1.25 on MCF-7 cells.The results of in vivo tumor suppression assay showed that the tumor growth inhibition rate in the HNTs-PEG-FA/Cur combined with radiotherapy group(56.75%)>radiation alone group(24.16%)>drug alone group(6.67%).Conclusion:As a new nano drug carrier of curcumin,HNTs-PEG-FA can effectively improve the bioavailability of curcumin and has the potential of targeted radiosensitization for breast cancer.

关 键 词：埃洛石纳米管 姜黄素 乳腺癌 放射增敏 

分 类 号：R737.9[医药卫生—肿瘤]