上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2020, Vol. 40 ›› Issue (4): 450-.doi: 10.3969/j.issn.1674-8115.2020.04.006

• 论著·基础研究 • 上一篇    下一篇

基于单壁碳纳米管的化学 - 光热协同治疗去势抵抗性前列腺癌的研究

宋绪佳1，张时君2，吕文鑫1，黄 林1，张 言1，吴明贵1，谢少伟2   

  1. 1. 广西壮族自治区柳州市工人医院，广西医科大学第四附属医院泌尿外科，柳州545005；2. 上海交通大学医学院附属仁济医院超声医学科，上海200127
  • 出版日期:2020-04-28 发布日期:2020-05-22
  • 通讯作者: 吴明贵，电子信箱：wuminggui1968@163.com。谢少伟，电子信箱：shaoweixie@yeah.net。为共同通信作者。
  • 作者简介:宋绪佳（1982—），男，主治医师，学士；电子信箱：147004633@qq.com。
  • 基金资助:
    国家自然科学基金（81901747）；上海市科学技术委员会研究项目（15411966300）。

Synergistic chemo-photothermal therapy of castration-resistant prostate cancersingle-walled carbon nanotube

SONG Xu-jia, ZHANG Shi-jun, Lü Wen-xin, HUANG Lin, ZHANG Yan, WU Ming-gui, XIE Shao-wei   

  1. 1. Department of Urology, Liuzhou Worker′s Hospital, the Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou 545005, China; 2. Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2020-04-28 Published:2020-05-22
  • Supported by:
    National Natural Science Foundation of China (81901747); Fund Science and Technology Commission of Shanghai Municipality (15411966300).

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摘要： 目的·研究基于单壁碳纳米管（single-walled carbon nanotubes，SWCNTs）的化学 - 光热协同治疗在增敏去势抵抗性前列腺癌（castration-resistant prostate cancer，CRPC）化学治疗（化疗）效果中的价值。方法·以高纯SWCNTs为载体，首先通过混酸处理，使其成为被截短的SWCHTs（shorten SWCNTs，s-SWCNTs）的同时，在其侧链及表面引入大量-COOH；随后在N- 羟基琥珀酰亚胺和1-(3-二甲氨基丙基)-3- 乙基碳二亚胺盐酸盐溶液中通过聚乙二醇（polyethylene glycol，PEG）的氨基端与s-SWCNTs表面的 -COOH形成酰胺键从而使PEG修饰在SWCNTs上，以赋予其水溶性及生物相容性。最后，多西他赛（docetaxel，DTX）通过纳米沉积方法与s-SWCNTs表面形成π-π堆积而成功负载后，一种同时具有化疗和光热特性的纳米系统被建立。体外实验评估化疗和光热对CRPC细胞系C4-2的协同抑制作用及体内抑瘤效果。结果·傅里叶变换红外光谱及zeta电位表明，-COOH被成功地引入s-SWCNTs中，并通过自动电导滴定测定得到每克SWCNTs所含-COOH的量为0.412 mol。紫外吸收光谱图表明DTX成功被负载到纳米材料上，通过监测透析液的紫外吸收确定了每毫克s-SWCNTs可负载高达1.35 mg的DTX；在酸性条件下，DTX可从材料表面迅速释放。体外光热、DTX及两者协同杀伤C4-2细胞的能力评估结果表明，联合治疗的效果大于单一治疗模式，并且在体内C4-2移植瘤模型小鼠中得到验证。结论·成功负载DTX的s-SWCNTs纳米系统表现出较高的稳定性和光热效应，能够抑制CRPC细胞及荷瘤小鼠肿瘤的生长。该纳米系统可实现化疗-光热协同作用，用于增敏化疗药物对前列腺肿瘤进行治疗。

关键词: 前列腺癌, 化学治疗, 纳米载体, 协同治疗

Abstract:

Objective · To study the synergistic effect of chemo-photothermal on castration-resistant prostate cancer (CRPC) for enhancing the efficacy of chemotherapysingle-walled carbon nanotubes (SWCNTs). Methods · High-purity SWCNTs were used as the drug carrier. Firstly, SWCHTs were truncated (shorten SWCNTs, s-SWCNTs)mixed acid solutions. At the same time, a large amount of -COOH were introduced onto the surface of s-SWCNTs. Secondly, the polyethylene glycol (PEG) with amino terminated was successfully modified onto s-SWCNTs through amido linkage in N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride solutions to endow s-SWCNTs with water solubility and biocompatibility. Finally, docetaxel (DTX) was successfully loaded through nano-deposition method and π-π stacking on the surface of s-SWCNTs. Thus a nanosystem with both chemotherapy and photothermal properties was established. The chemo-photothermal therapy synergistic inhibition on CRPC cell line C4-2 in vitro and the anti-tumor effect in vivo were evaluated. Results · Fourier transform infrared spectrum and zeta potential test showed that -COOH was successfully introduced onto s-SWCNTs, and the amount of -COOH was 0.412 mol per gram of SWCNTs determinedautomatic conduct metric titration. The UV absorption spectrum showed that DTX was successfully loaded onto the nanosystem.monitoring the UV absorption of the dialysate, DTX could be loaded onto SWCNTs up to 1.35 mg per gram of s-SWCNTs. Under the stimulation of acidic conditions, DTX could be rapidly released the surface of the nanosystem. The in vitro cell viability and in vivo anti-tumor experiment showed that DTX combined with photothermal had a synergetic effect on killing C4-2 cells than any single treatment model. Conclusion · DTX-loaded s-SWCNTs nanosystem with high stability and photothermal effect can inhibit the growth of CRPC cells and the tumor growth in mice bearing CRPC. The nanosystem with synergistic effect of chemotherapy and photothermal therapy could be used in the treatment of prostate cancer which is resistant to chemotherapy drugs.

Key words: prostate cancer, chemotherapy, nanocarriers, synergistic therapy