Au_(25)(Capt)_(18)纳米簇介导近红外光触发光热-光动力抗皮肤鳞状细胞癌体外研究  

In Vitro Evaluation of Anti-Cutaneous Squamous Cell Carcinoma Effect of Photothermal and Photodynamic Therapy with Near-Infrared Light Mediated by Au_(25)(Capt)_(18)-Nanocluster

作　　者：刘沛 石磊[2] 张海艳[2] 张付贺[2] 文龙 杨维涛 余佳霓 王秀丽 魏志平[1] LIU Pei;SHI Lei;ZHANG Haiyan;ZHANG Fuhe;WEN Long;YANG Weitao;YU Jiani;WANG Xiuli;WEI Zhiping(Department of Dermatology, Affiliated Hospital of Xuzhoa Medical College, Xuzhou 221002, China;Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China)

机构地区：[1]徐州医科大学附属医院皮肤科,江苏徐州221002 [2]上海市皮肤病医院、同济大学医学院光医学研究所,上海200443

出　　处：《中国皮肤性病学杂志》2018年第7期741-746,共6页The Chinese Journal of Dermatovenereology

基　　金：国家自然基金项目(81601601,81472538)

摘　　要：目的构建Au_(25)(Capt)_(18)纳米簇介导近红外光触发光热-光动力治疗体系,并研究其对皮肤鳞癌的体外杀伤作用。方法采用一锅法制备Au_(25)(Capt)_(18)纳米簇,透射电镜表征Au_(25)(Capt)_(18)的粒径、分散性,紫外-可见吸收光谱法检测Au_(25)(Capt)_(18)发光性能。以紫外线诱导成瘤的SKH-1皮肤鳞癌小鼠的原代鳞癌细胞为研究对象,Cell Counting Kit-8(CCK-8)法检测Au_(25)(Capt)_(18)对鳞癌原代细胞的毒性。将小鼠鳞癌原代细胞分为光热-光动力治疗组、单光组、单药组、空白组,给予相应处理,24h后观察各组细胞形态学变化,CCK-8法检测各组处理对细胞的增殖抑制作用,热成像仪监测细胞温度变化评价光热效应,SOSGR单线态氧指示剂检测单线态氧产出量评价光动力效应。结果合成的Au_(25)(Capt)_(18)纳米簇,粒径2~3nm,分散均匀,在近红外光区域有强吸收。Au_(25)(Capt)_(18)在Au浓度范围为0~80μg/m L时对小鼠皮肤鳞癌原代细胞无毒;各组相应处理后,光热-光动力治疗组细胞存活率为(44.30±9.30)%,显著低于单光组、单药组、空白组(P均<0.01)。光热-光动力治疗组照光后细胞温度可达(43.43±1.17)℃,显著高于单光组、单药组、空白组(P均<0.01)。光热-光动力治疗组照光后细胞单线态氧荧光强度与空白组相比的相对值为(3.03±0.48),显著高于单光组、单药组、空白组(P均<0.01)。结论 808nm激光照射Au_(25)(Capt)_(18)可同时产生光热和光动力效应,对皮肤鳞癌原代细胞具有安全有效的增殖抑制作用。Objective To establish a photothermal-photodynamic therapy system with near-infra- red light mediated by Au25 （Capt）18-nanocluster, and to investigate its efficacy against cutaneous squamous cell carcinoma （cSCC） in vitro. Methods The Au25 （Capt） 18 was prepared by one-pot method. The particle size and luminescence property of Au25 （Capt） 18 were characterized by transmission electron microscopy and ultraviolet-visi- ble （UV-vis） spectrometry. Cell Counting Kit-8 （CCK-8） method was used to detect the toxicity of Au25 （Capt） 18 on cSCC primary cells from ultraviolet induced SKH-1 SCC mice. Primary cSCC cells were divided into four groups： photothermal-photody- namic therapy （VVF-PDT） group, 808 nm laser group, Au25 （Capt）18group and con- trol. In addition to assess changes in cell morphology, cell viabilities were measured using CCK-8 method 24 hours after treatment. Changes in temperature of cells during the treatment were detected using infrared thermal imaging to evaluate the PTT effect. The singlet oxygen （102 ） generation of cells was assessed by singlet oxygen sensor green reagent （SOSGR） to evaluate the PDT effect. Results Au25 （Capt）18, uni- formly dispersed, was about 2 - 3 nm in diameter and showed strong absorption in the near-infrared region. Au25 （Capt）18 at concentrations of 0 -80μg/mL Au was nontox- ic to cSCC cells. Following treatment, cell viability in PTT-PDT group was signifi- cantly lower than that in other groups （P 〈 0. 01 ）. In contrast, temperature of cells in PTT-PDT group was much higher than that in other groups （P 〈 0. 01 ）. Similarly, relative singlet oxygen fluorescence intensity in PTT-PDT group was higher than that in other groups （ P 〈 0. 01 ）. Conclusion Photothermal and photodynamic therapy induced by irradiation of Au25 （Capt） 18-nanocluster with 808nm near-infrared light is safe and effective in inhibition of primary cSCC cells.

关 键 词：鳞状细胞癌 金纳米 近红外光 光热治疗 光动力治疗 

分 类 号：R739.5[医药卫生—肿瘤]