口腔医学研究

口腔医学研究 ›› 2025, Vol. 41 ›› Issue (4): 293-300.DOI: 10.13701/j.cnki.kqyxyj.2025.04.005

• 口腔颌面肿瘤学研究 • 上一篇    下一篇

增溶性紫杉醇聚合物胶束抗口腔鳞状细胞癌的实验研究

杨昊楠1,2, 刘丰1,2, 孟箭1,2,3*, 周霖2,3, 戴雨薇1,2, 陈寅瑜2,3   

  1. 1.山东第二医科大学口腔医学院 山东 潍坊 261000;
    2.徐州市中心医院口腔科 江苏 徐州 221000;
    3.徐州医科大学口腔医学院 江苏 徐州 221000
  • 收稿日期:2024-10-23 发布日期:2025-04-24
  • 通讯作者: * 孟箭,E-mail:mrocket@126.com
  • 作者简介:杨昊楠(1997~ ),女,黑龙江人,硕士在读,主要从事口腔颌面外科相关研究。
  • 基金资助:
    国家口腔疾病临床医学研究中心开放课题(编号:NCRCO-202101); 徐州医科大学附属医院发展基金项目(编号:XYFY202207)

Preparation of Paclitaxel Polymer Micelles and Its Anti-oral Squamous Cell Carcinoma Effect

YANG Haonan1,2, LIU Feng1,2, MENG Jian1,2,3*, ZHOU Lin2,3, DAI Yuwei1,2, CHEN Yinyu2,3   

  1. 1. School of Stomatology, Shandong Second Medical University, Weifang 261000, China;
    2. Department of Stomatology, Xuzhou Central Hospital, Xuzhou 221000, China;
    3. School of Stomatology, Xuzhou Medical University, Xuzhou 221000, China
  • Received:2024-10-23 Published:2025-04-24

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摘要： 目的: 为提高紫杉醇(paclitaxel,PTX)的水溶性及对肿瘤的被动靶向作用,设计并合成两亲性聚乙二醇(polyethylene glycol,PEG)-十八胺嵌段共聚物,形成包裹PTX的聚合物胶束,并探索其抗肿瘤活性。方法: 用薄膜分散法制备包覆PTX的PEG-十八胺聚合物胶束(polyethylene glycol-octadecylamine polymer micelles-paclitaxel,PEG-ODA-PTX),并对其粒径和Zeta电位、包封率、透射电子显微镜(transmission election microscope,TEM)微观形态及稳定性进行考察。通过细胞摄取、CCK-8法及活/死细胞染色实验,在细胞水平检测其抗肿瘤效应及细胞毒性。构建裸鼠CAL-27细胞移植瘤模型,检测其体内抗肿瘤效果及生物安全性。结果: 结果显示PEG-ODA-PTX粒径为(188.4±7.9) nm,电位为(28.50±0.1) mV,包封率为(76.43±1.2)%、TEM下观察为大小均一的球状结构,稳定性良好。PEG-ODA-C6对CAL-27细胞具有显著的靶向作用,且PEG-ODA-PTX对CAL-27细胞的增殖具有显著的抑制作用,可诱导细胞凋亡。与对照组相比,PEG-ODA-PTX可显著减小裸鼠瘤体体积(P＜0.05),抑瘤率达到72%。溶血实验、细胞毒性实验以及苏木精-伊红染色实验证实PEG-ODA-PTX具有较好的生物安全性。结论: 本实验成功制备聚合物胶束PEG-ODA-PTX,其具有显著的口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)细胞靶向性,并在细胞水平和整体动物水平均表现出优良的抗OSCC效应。

关键词: 聚乙二醇, 十八胺, 紫杉醇, 聚合物胶束, 口腔鳞状细胞癌

Abstract: Objective: To improve the water solubility of paclitaxel(PTX) and passive targeting of tumor by designing amphiphilic PEG-octadecamine block copolymers to form polymer micelles and encapsulating with PTX, and to explore its anti-tumor activity. Methods: PEG-octadecylamine polymer micelles (PEG-ODA-PTX) were coated with PTX by thin-film dispersion method.The particle size, Zeta potential, encapsulation rate, transmission electron microscopy (TEM) images, and stability of the PEG-ODA-PTX were investigated. The anti-tumor effect and cytotoxicity were detected by cell uptake evaluation, CCK-8 assay, and live/dead cell staining method. CAL-27 cells were used to construct a nude mouse transplanted tumor model, and its anti-tumor effect and biosafety were tested. Results: The particle size and Zeta potential of PEG-ODA-PTX were (188.4±7.9) nm and (28.50±0.1) mV, respectively. The encapsulation rate of PTX was about (76.43±1.2)%. Spherical structure with uniform size was observed under TEM. PEG-ODA-PTX showed good stability in 24 h. PEG-ODA-C6 could be specifically internalized by CAL-27 cells. PEG-ODA-PTX significantly inhibited the proliferation of CAL-27 cells and induced cell apoptosis. Compared with the control group, PEG-ODA-PTX significantly reduced the tumor volume in nude mice (P<0.05) and the tumor suppression rate reached 72%. Hemolysis, cytotoxicity, and H&E staining experiments confirmed the biosafety of PEG-ODA-PTX. Conclusion: The polymer micelles PEG-ODA-PTX was successfully prepared and showed significant targeting towards oral squamous cancer cells, which had excellent anti-oral squamous cell carcinomaeffect at both cellular and overall animal levels.

Key words: PEG, octadecylamine, paclitaxel, polymer micelles, oral squamous cell carcinom