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中华介入放射学电子杂志

中华介入放射学电子杂志 ›› 2022, Vol. 10 ›› Issue (02) : 131 -136. doi: 10.3877/cma.j.issn.2095-5782.2022.02.003

基础研究

经聚乙烯亚胺钝化的荧光碳点负载阿霉素抑制非小细胞肺癌细胞增殖、迁移侵袭的治疗研究
唐柯馨1, 林熙2, 单鸿3,†()   
  1. 1. 519000　广东珠海，中山大学附属第五医院介入医学中心；广东省生物医学影像重点实验室；广东省分子影像工程技术中心
    3. 广东省生物医学影像重点实验室；广东省分子影像工程技术中心
  • 收稿日期:2022-05-12 出版日期:2022-05-25
  • 通信作者: 单鸿
  • 基金资助:
    国家自然科学基金(81620108017)

Doxorubicin-loaded fluorescent carbon dots with PEI passivation inhibited proliferation, migration and invasion of non-small cell lung cancer cells

Kexin Tang1, Xi Lin2, Hong Shan3,†()   

  1. 1. Center of Interventional Medicine, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China; Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China; Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China
    2. Center of Interventional Medicine, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China; Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China; Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China.
    3. Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China; Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Zhuhai 519000, China
  • Received:2022-05-12 Published:2022-05-25
  • Corresponding author: Hong Shan
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唐柯馨, 林熙, 单鸿. 经聚乙烯亚胺钝化的荧光碳点负载阿霉素抑制非小细胞肺癌细胞增殖、迁移侵袭的治疗研究[J/OL]. 中华介入放射学电子杂志, 2022, 10(02): 131-136.

Kexin Tang, Xi Lin, Hong Shan. Doxorubicin-loaded fluorescent carbon dots with PEI passivation inhibited proliferation, migration and invasion of non-small cell lung cancer cells[J/OL]. Chinese Journal of Interventional Radiology(Electronic Edition), 2022, 10(02): 131-136.

目的

研究利用经聚乙烯亚胺（PEI）钝化的荧光碳点（CD）装载阿霉素（DOX）进行药物递送，旨在增加DOX对非小细胞肺癌的治疗作用，减少DOX的心肌毒性。

方法

通过一步微波加热法将甘油和PEI的混合物制备成CD-PEI，并通过静电效应将DOX装载至CD-PEI。采用CCK8实验检测CD-PEI-DOX对非小细胞肺癌细胞A549的增殖能力的影响；Transwell实验评估CD-PEI-DOX对A549细胞迁移侵袭能力的影响；最后通过体内动物实验评估CD-PEI-DOX的心肌毒性以及对非小细胞肺癌皮下肿瘤生长的抑制效果。

结果

体外细胞实验证实，对比单纯的DOX处理组，CD-PEI-DOX对非小细胞肺癌A549细胞增殖、迁移侵袭能力的抑制作用更为显著。体内实验证实，CD-PEI-DOX纳米复合物治疗组小鼠心肌细胞结构完整，并且能有效抑制小鼠皮下肺癌肿瘤的生长。

结论

经PEI钝化的荧光碳点负载阿霉素能显著提高DOX对非小细胞肺癌的治疗效果，并减少DOX对心脏的毒性作用。运用CD-PEI纳米颗粒改善化疗药物递送的治疗方案取得了初步证实，这可为肺癌化学治疗提供新思路，具有广大的临床应用前景。

关键词: 阿霉素, 纳米载体, 荧光碳点, 非小细胞肺癌
Objective

Aims to use polyethylenimine (PEI) passivated fluorescent carbon dots (CD) loaded doxorubicin (DOX) for drug delivery, so as to increase the therapeutic effect of DOX on non-small cell lung cancer and reduce the cardiotoxicity.

Methods

CD-PEI was synthesized by the one-step microwave hydrothermal carbonization of a mixture of glycerol and PEI, and DOX was loaded onto CD-PEI by electrostatic interactions. The effect of CD-PEI-DOX on proliferation of non-small cell lung cancer cells A549 was detected by CCK8 assay.The migration and invasion of A549 cells was evaluated by Transwell assay. Finally, the cardiotoxicity of CD-PEI-DOX and its inhibitory effect on subcutaneous tumor growth of non-small cell lung cancer were evaluated by in vivo animal experiments.

Results

In vitro cell experiments confirmed that CD-PEI-DOX had a more significant inhibitory effect on the proliferation, migration and invasion of non-small cell lung cancer A549 cells compared with the simple DOX treatment group. In vivo experiments confirmed that the cardiomyocyte structure of mice in the CD-PEI-DOX nanocomposite treatment group was complete, and the CD-PEI-DOX could effectively inhibit the growth of subcutaneous lung cancer tumors in mice.

Conclusions

Doxorubicin-loaded fluorescent carbon dots passivated by PEI can significantly improve the therapeutic effect of DOX on non-small cell lung cancer and reduce the cardiotoxic effect of DOX. The use of CD-PEI nanoparticles to improve the delivery of chemotherapeutic drugs has been preliminarily confirmed, This can provide new ideas for chemotherapy of lung cancer and has broad clinical application prospects.

Key words: Doxorubicin, Nanocarriers, Fluorescent carbon dots, Non-small cell lung cancer
图1 CD-PEI和CD-PEI-DOX的基本性质1A：CD-PEI纳米颗粒的TEM图像；1B：CD-PEI、游离DOX、CD-PEI-DOX的Zeta点位（比例尺为5 nm）。
图2 指定溶度下CD-PEI、游离DOX以及CD-PEI-DOX对A549细胞的增殖活性的影响情况2A：指定浓度下CD-PEI对A549细胞增殖活性的影响；2B：指定浓度下游离DOX、CD-PEI-DOX与A549细胞共孵育24 h后的细胞活性情况，*表示P < 0.05，**表示P < 0.01，***表示P < 0.001。
图3 游离DOX和CD-PEI-DOX对A549细胞迁移侵袭能力的影响情况3A：A549细胞迁移和侵袭至Transwell小室下层膜的细胞图像；3B：游离DOX和CD-PEI-DOX处理组对A549细胞迁移侵袭抑制率的量化分析，***表示P < 0.001（比例尺为200 μm）。
图4 游离DOX和CD-PEI-DOX的心肌毒性及体内肿瘤抑制效果4A：不同药物处理21 d后小鼠心脏组织HE染色图片；4B：不同药物治疗21 d小鼠皮下瘤的生长情况（比例尺为20 μm）。
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