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.
作者
王寒剑
韩栋梁
危文祥
田卫群
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)
出处
《现代肿瘤医学》
CAS
北大核心
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)。
关键词
埃洛石纳米管
姜黄素
乳腺癌
放射增敏
halloysite nanotubes
curcumin
breast cancer
radiosensitization
