姜黄素碳点研制及声动力治疗动脉粥样硬化的效应评估  

Preparation of curcumin-derived carbon dots and evaluation of sonodynamic therapy in atherosclerosis

作　　者：陈粤瑛 周世源 桂斌 郭宇昕 刘乾辉 蒲欢 潘桔红 周青[1] Chen Yueying;Zhou Shiyuan;Gui Bin;Guo Yuxin;Liu Qianhui;Pu Huan;Pan Juhong;Zhou Qing(Department of Ultrasonography,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院超声影像科,武汉430060

出　　处：《中华超声影像学杂志》2024年第10期899-910,共12页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金(82271999)。

摘　　要：目的姜黄素是天然存在于姜黄中的多酚类化合物,可作为一种声敏剂用于声动力治疗动脉粥样硬化,然而水溶性差、生物利用度低等缺陷限制了其声动力的疗效。本研究拟将姜黄素转化为姜黄素碳点(Cur-CDs),提高水溶性、生物相容性、荧光性和声敏性,以提升声动力治疗(SDT)的效果。方法采用水热法合成Cur-CDs,透射电子显微镜观察形貌,傅里叶变换红外光谱仪和X射线光电子能谱仪分析化学组成和表面官能团,紫外分光光度计和荧光光谱分析光学性质,细胞增殖与活力实验和溶血实验检测生物相容性。通过检测Cur-CDs生成活性氧的水平以评估Cur-CDs的声敏性。实时荧光定量聚合酶链式反应检测M1型、M2型巨噬细胞标志基因,以验证Cur-CDs介导的SDT对巨噬细胞表型的作用。通过活体荧光成像、离体主动脉荧光成像,评估Cur-CDs的斑块检测性能。将斑块小鼠分成5组:①对照组、②姜黄素组、③Cur-CDs组、④姜黄素+低强度脉冲超声(LIPUS)组、⑤Cur-CDs+LPIUS组,通过主动脉油红O染色、检测血脂水平,评估SDT疗效。结果成功制备Cur-CDs,粒径(1.87±0.35)nm,具有球形形态和明显的晶格条纹。Cur-CDs含有丰富的含氧亲水官能团,水溶解度约是姜黄素的105倍。Cur-CDs有很好的生物相容性,浓度500 mg/L以内Cur-CDs对细胞增殖与活力无明显影响,溶血率<1%,溶血性可忽略不计。Cur-CDs具备良好且稳定的荧光性能,最大激发波长和发射波长分别是420 nm、530 nm,能进行斑块荧光成像,且在斑块处的荧光强度远大于姜黄素(P<0.01)。Cur-CDs被LIPUS激活可产生1O_(2)、·OH和·O_(2)^(-),生成的活性氧总量大于姜黄素(P<0.05)。Cur-CDs介导的SDT促进巨噬细胞从M1型向M2型转化,其效果优于姜黄素介导的SDT。油红O染色显示,Cur-CDs+LIPUS组的斑块面积和脂质含量最低,其效果约是姜黄素+LIPUS组的3倍,证明Cur-CDs介导的SDT疗效更显著。结论�Objective To improve the aqueous solubility,biocompatibility,fluorescence,and sonosensitivity of curcumin,this study aims to transform curcumin into curcumin-derived carbon dots(Cur-CDs)to enhance the efficacy of sonodynamic therapy(SDT)of atherosclerosis(AS).MethodsCur-CDs were synthesized via a hydrothermal method.The morphology was characterized by transmission electron microscopy,while Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were applied to analyze the chemical composition and surface functional groups.Optical properties were examined by UV-visible spectrophotometry and fluorescence spectroscopy.Cell proliferation and viability assay and a hemolysis experiment were performed to assess biocompatibility.The sonosensitivity of Cur-CDs was determined by the measurement of reactive oxygen species(ROS)produced by Cur-CDs.To verify the effect of Cur-CDs-mediated SDT on macrophage phenotype,the M1 and M2 macrophage marker genes were detected via real-time fluorescence quantitative polymerase chain reaction.The ability of Cur-CDs in plaque detection was assessed through in vivo fluorescence imaging and ex vivo aortic fluorescence imaging.Atherosclerotic plaque mice were divided into five groups:control group,curcumin group,Cur-CDs group,curcumin+low-intensity pulsed ultrasound(LIPUS)group,and Cur-CDs+LPIUS group.Aortic Oil red O staining and blood lipid level measurements were conducted to evaluate the therapeutic efficacy of SDT on the plaques.ResultsCur-CDs exhibited a spherical morphology and a distinct lattice structure with the diameter of(1.87±0.35)nm.The aqueous solubility of Cur-CDs was about 105 times that of curcumin because of their abundant oxygen-containing hydrophilic functional groups.Cur-CDs at concentrations up to 500 mg/L had no significant impact on cell proliferation and viability,with a negligible hemolysis rate of<1%,indicating good biocompatibility of Cur-CDs.Cur-CDs exhibited a stable and excellent fluorescence with the maximum excitation and emission wavel

关 键 词：动脉粥样硬化 声动力治疗 姜黄素 碳点 

分 类 号：R543.5[医药卫生—心血管疾病]