南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (12): 1843-1849.doi: 10.12122/j.issn.1673-4254.2021.12.13

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纳米硫化铜复合物光热治疗对舌鳞状细胞癌的体内外抑制作用

陈 栋，陈之锋，王 邹，杨雅洁，蒋艳萍，胡 琛   

  1. 南方医科大学南方医院口腔科，广东 广州 510515
  • 出版日期:2021-12-20 发布日期:2022-01-04

Photothermal effect of nano-copper sulfide against tongue squamous cell carcinoma

CHEN Dong, CHEN Zhifeng, WANG Zou, YANG Yajie, JIANG Yanping, HU Chen   

  1. Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • Online:2021-12-20 Published:2022-01-04

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摘要： 目的 探讨BSA@CuS-PEG纳米复合物的制备、表征、功能及其对舌癌的抗肿瘤效应的作用。方法 采用透射电镜，动态光散射，Zeta电位分析及紫外吸收光谱分析方法分析BSA@CuS-PEG纳米复合物的表征，利用近红外II区激发光（1064 nm）探究其光热性能，同时采用CCK-8实验评估该纳米复合物的细胞毒性，流式细胞学实验分析细胞周期分布水平。最后，构建单侧皮下荷瘤模型探究BSA@CuS-PEG纳米复合物的体内抗肿瘤作用。结果 成功制备BSA@CuS-PEG纳米复合物，在0.5 W/cm2功率的近红外光照射下其变化温度值（ΔT）约为30 ℃，具有优良的光热性能。CCK8实验表明：单纯BSA@CuS-PEG对肿瘤细胞无明显毒性；而相比于纯材料组，BSA@CuS-PEG联合近红外光照射对Cal27及SCC9舌癌细胞具有显著抑制增殖作用（P<0.001）。同时细胞周期分析显示：相比于纯材料组，BSA@CuS-PEG联合近红外光照射使Cal27及SCC9舌癌细胞更多被阻滞于G2/M期（P<0.001）。小鼠单侧皮下荷瘤模型表明：相比于生理盐水联合近红外光照射处理组，BSA@CuS-PEG联合近红外光照射发挥显著的体内抗肿瘤作用（P<0.001）。结论 BSA@CuS-PEG纳米复合物具有良好的光热效应，体内外抗肿瘤效应，为舌癌原发灶无创早期诊断和非手术治疗提供一种潜在思路和手段。

关键词: 光热治疗；硫化铜；舌癌；纳米复合物

Abstract: Objective To investigate the anti-tumor effect of BSA@CuS-PEG nanocomposites on tongue squamous cell carcinoma. Methods Transmission electron microscopy, dynamic light scattering, Zeta potential and ultraviolet absorption spectroscopy were used to characterize the synthesized BSA@CuS-PEG nanocomposite, whose photothermal properties was assessed with near infrared II region excitation light (1064 nm). The cytotoxicity of the nanocomposite in Cal27 and SCC9 cells was evaluated using CCK-8 assay, and its effect on cell cycle distribution was analyzed using flow cytometry. The in vivo antitumor effect of BSA@CuS-PEG was investigated in a Balb/c mouse model bearing subcutaneous Cal27 tumor xenograft. Results The synthesized BSA@CuS-PEG nanocomposite showed a temperature variation (ΔT) of about 30 ℃ under near-infrared (NIR) irradiation (0.5 W/cm2), suggesting its excellent photothermal sensitivity. CCK-8 assay showed that BSA@CuS-PEG had no significant toxicity to tumor cells, but upon NIR irradiation, the nanocomposite produced a significant stronger inhibitory effect on Cal27 and SCC9 cells than free nanocomposites (P<0.001). Cell cycle analysis showed that compared with free nanocomposites, BSA@CuS-PEG plus NIR irradiation caused more obvious cell cycle arrest at G2/M phase in tongue cancer cells (P<0.001). In the tumor-bearing mice, BSA@CuS-PEG combined with NIR irradiation produced a significant anti-tumor effect as compared with saline treatment plus NIR irradiation (P<0.001). Conclusion The BSA@CuS-PEG nanocomposite shows prominent photothermal properties and good anti-tumor effects both in vivo and in vitro, and thus provides a promising method for non-invasive early diagnosis and non-surgical treatment of primary tongue cancer.

Key words: photothermal therapy; copper sulfide; tongue cancer; nanocomposites