增溶性紫杉醇聚合物胶束抗口腔鳞状细胞癌的实验研究  

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

作　　者：杨昊楠 刘丰 孟箭 周霖[2,3] 戴雨薇 陈寅瑜 YANG Haonan;LIU Feng;MENG Jian;ZHOU Lin;DAI Yuwei;CHEN Yinyu(School of Stomatology,Shandong Second Medical University,Weifang 261000,China;Department of Stomatology,Xuzhou Central Hospital,Xuzhou 221000,China;School of Stomatology,Xuzhou Medical University,Xuzhou 221000,China)

机构地区：[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

出　　处：《口腔医学研究》2025年第4期293-300,共8页Journal of Oral Science Research

基　　金：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)。

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。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.

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 

分 类 号：R739.8[医药卫生—肿瘤]