切换至 "中华医学电子期刊资源库"
高级检索
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
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

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]. 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]. 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）。
[1]
Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1): 7-33.
[2]
Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention[J]. Clin Chest Med, 2011, 32(4): 605-644.
[3]
Hanna NH, Schneider BJ, Temin S, et al. Therapy for stage IV non-small-cell lung cancer without driver alterations: ASCO and OH (CCO) joint guideline update[J]. J Clin Oncol, 2020, 38(14): 1608-1632.
[4]
Kris M, Gaspar L, Chaft J, et al. Adjuvant systemic therapy and adjuvant radiation therapy for stage I toⅢA completely resected non-small-cell lung cancers: American society of clinical oncology/cancer care ontario clinical practice guideline update[J]. J Clin Oncol, 2017, 35(25): 2960-2974.
[5]
Daly M, Singh N, Ismaila N, et al. Management of stage Ⅲ non-small-cell lung cancer: ASCO guideline[J]. J Clin Oncol, 2022, 40(12): 1356-1384.
[6]
Osataphan N, Phrommintikul A, Chattipakorn S, et al. Effects of doxorubicin-induced cardiotoxicity on cardiac mitochondrial dynamics and mitochondrial function: Insights for future interventions[J]. J Cell Mol Med, 2020, 24(12): 6534-6557.
[7]
Patra J, Das G, Fraceto L, et al. Nano based drug delivery systems: recent developments and future prospects[J]. J Nanobiotechnology, 2018, 16(1): 71.
[8]
Hong G, Diao S, Antaris A, et al. Carbon nanomaterials for biological imaging and nanomedicinal therapy[J]. Chem Rev, 2015, 115(19): 10816-10906.
[9]
Zeng Q, Shao D, He X, et al. Carbon dots as a trackable drug delivery carrier for localized cancer therapy in vivo[J]. J Mater Chem B, 2016, 4(30): 5119-5126.
[10]
Tang J, Kong B, Wu H, et al. Carbon nanodots featuring efficient FRET for real-time monitoring of drug delivery and two-photon imaging[J]. Adv Mater, 2013, 25(45): 6569-6574.
[11]
Karthik S, Saha B, Ghosh S, et al. Photoresponsive quinoline tethered fluorescent carbon dots for regulated anticancer drug delivery[J]. Chem Commun (Camb), 2013, 49(89): 10471-10473.
[12]
Baker S, Baker G. Luminescent carbon nanodots: emergent nanolights[J]. Angew Chem Int Ed Engl, 2010, 49(38): 6726-6744.
[13]
Liu C, Zhang P, Zhai X, et al. Nano-carrier for gene delivery and bioimaging based on carbon dots with PEI-passivation enhanced fluorescence[J]. Biomaterials, 2012, 33(13): 3604-3613.
[14]
Hou J, Yan J, Zhao Q, et al. A novel one-pot route for large-scale preparation of highly photoluminescent carbon quantum dots powders[J]. Nanoscale, 2013, 5(20): 9558-9561.
[15]
Yang L, Wang Z, Wang J, et al. Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy[J]. Nanoscale, 2016, 8(12): 6801-6809.
[16]
Yu H, Lv X, Wu L, et al. Doxorubicin-loaded fluorescent carbon dots with PEI passivation as a drug delivery system for cancer therapy[J]. Nanoscale, 2020, 12(33): 17222-17237.
[17]
Xu J, Sahu S, Cao L, et al. Carbon nanoparticles as chromophores for photon harvesting and photoconversion[J]. Chemphyschem, 2011, 12(18): 3604-3608.
[18]
Lages E, Fernandes R, Silva J, et al. Co-delivery of doxorubicin, docosahexaenoic acid, and α-tocopherol succinate by nanostructured lipid carriers has a synergistic effect to enhance antitumor activity and reduce toxicity[J]. Biomed Pharmacother, 2020, 132: 110876.
[19]
Sohail M, Sun Z, Li Y, et al. Research progress in strategies to improve the efficacy and safety of doxorubicin for cancer chemotherapy[J]. Expert Rev Anticancer Ther, 2021, 21(12): 1385-1398.
[1] 顾志波, 郝林, 陆明, 陈建刚. 光动力纳米载体联合si-P3H4治疗膀胱癌的初步探索[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(06): 633-641.
[2] 朱超男, 王帅, 王文博, 郑贸根, 程远, 陈志全. 非小细胞肺癌患者组织miR-31-5p表达与临床病理特征及预后的关系[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 508-510.
[3] 陈坤, 何傅梅, 方婷, 陈文瑞. 血清sCD73与EGFR/ALK野生型非小细胞肺癌免疫治疗效果的相关性分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 504-507.
[4] 黄承路, 廖飞, 刘显平, 王志强. 血清外泌体Has_circ_0060937过度表达与NSCLC转移和不良预后的关系[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 490-494.
[5] 徐天亮, 程干思, 吴亚平, 龚荣, 胡洁, 段群娣, 李承慧. 奥希替尼联合安罗替尼二线治疗转移性NSCLC的疗效分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 520-522.
[6] 魏婷婷, 胡小红, 龚自强, 熊鹿. 老年非小细胞肺癌组织ARPC2表达及与预后关系[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 584-586.
[7] 杜静怡, 徐兴祥. 循环肿瘤细胞在非小细胞肺癌中的研究进展[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 596-600.
[8] 杨豪, 王云川, 陈有英. 硬膜外阻滞复合羟考酮镇痛在非小细胞肺癌患者中的应用[J]. 中华肺部疾病杂志(电子版), 2023, 16(03): 370-372.
[9] 李咏生, 孙建国, 李梦侠, 重庆肺癌精准治疗协作组(CPLOG). 第三代EGFR-TKI耐药后诊疗策略专家共识[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 145-155.
[10] 李多, 郝昭昭, 陈延伟, 南岩东. Wnt/β-Catenin通路促进非小细胞肺癌转移机制研究进展[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 281-284.
[11] 邹琴, 龙玲, 叶容, 张小洪. PD-1抑制剂免疫治疗NSCLC所致反应性毛细血管增生症的研究进展[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 278-280.
[12] 仇丽敏, 胡航, 孙云浩, 孙健, 陈婷婷. NSCLC患者根治性切除术后复发风险分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 242-244.
[13] 李一然, 王玉秀, 朱研, 王梦, 刘颖, 闫文锦, 徐兴祥, 闵凌峰. 基于GEO数据库分析影响纳武单抗及派姆单抗治疗非小细胞肺癌疗效的差异基因[J]. 中华肺部疾病杂志(电子版), 2023, 16(01): 20-25.
[14] 钱小卫, 丁海兵, 游继军, 王熠, 卞小霞. 微小miR水平联合检测在非小细胞肺癌转移中的意义[J]. 中华肺部疾病杂志(电子版), 2023, 16(01): 47-50.
[15] 蔡泽宇, 兰慧敏, 于婷, 罗慧. 基于Ti3C2负载阿霉素联合光热治疗抑制乳腺癌细胞增殖的研究[J]. 中华介入放射学电子杂志, 2023, 11(02): 140-145.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号