载紫杉醇聚(2-乙基-2-噁唑啉)修饰单壁碳纳米管递药系统的制备及体外抗肿瘤作用评价

目的 以抗肿瘤药物紫杉醇（PTX）为模型药物，制备载紫杉醇聚（2-乙基-2-噁唑啉）（PEOz）修饰单壁碳纳米管递药系统（PTX@PEOz-SWCNT），对其进行理化性质、体外释药、生物相容性及体外抗肿瘤作用的评价。方法 采用化学偶联合成PEOz-SWCNT，用紫外-可见吸收光谱法（UV-Vis）和红外光谱法（FTIR）对合成产物进行表征，并对其粒径和电位进行测定；制备载药复合物PTX@PEOz-SWCNT，测定其载药量和包封率，透析法进行体外释药试验；体外溶血试验评价载体材料的安全性，MTT法评价载体材料生物相容性及载药复合物对MCF-7细胞的生长抑制率，用荧光倒置显微镜考察了香豆素-6（C6）标记载体在MCF-7细胞中的摄取。结果 PEOz-SWCNT材料的平均粒径为（219.8±2.9）nm，Zeta电位值为（-35.23±0.74）mV，PTX@PEOz-SWCNT的载药量为（38.19±0.74）%，包封率为（94.38±0.94）%；载药复合物在pH 5.0的条件下释药明显加快，表现出明显的pH响应性；体外溶血试验结果表明，PEOz-SWCNT质量浓度在0.4 mg/mL以下无明显溶血反应，PEOz-SWCNT材料在细胞水平生物相容性良好，PTX@PEOz-SWCNT对MCF-7细胞的生长抑制率显著增强；与C6@SWCNT相比，C6@PEOz-SWCNT载药复合物的细胞摄取增加。结论 PTX@PEOz-SWCNT递药系统在肿瘤靶向给药方面具有一定的应用前景。

Preparation of PEOz-modified single-walled carbon nanotube paclitaxel delivery system and evaluation of its anti-tumor effect in vitro

Objective To prepare a PEOz modified single-walled carbon nanotube delivery system (PEOz-SWCNT) with the anti- tumor drug paclitaxel (PTX) as a model drug (PTX@PEOz-SWCNT) and evaluate its physical and chemical properties, in vitro drug release, biocompatibility, and in vitro antitumor effects. Methods PEOz-SWCNT was synthesized by chemical coupling method, and the products were characterized by UV-Vis spectroscopy (UV-Vis) and infrared spectroscopy (FTIR). The particle size and Zeta potential of PEOz-SWCNT were measured. The drug-loaded complex PTX@PEOz-SWCNT was prepared and the loading efficiency and encapsulation efficiency were measured. The dialysis method was used for in vitro drug release. The safety of the application of PEOz-SWCNT was evaluated by in vitro hemolysis test. The MTT method was used to evaluate the biocompatibility of the material and the growth inhibition rate of the drug-loaded complex on MCF-7 cells. The uptake of Coumarin-6 (C6)-labeled vector in MCF-7 cells was examined by fluorescence inversion microscope. Results The average particle size of PEOz-SWCNT was (219.8±2.9) nm and the Zeta potential was (-35.23±0.74) mV. The loading efficiency of PTX@PEOz-SWCNT was (38.19±0.74)%, and the encapsulation efficiency was (94.38±0.94)%. The drug release rate was significantly accelerated at pH 5.0, showing obvious pH responsiveness. There was no obvious hemolysis when the concentration of PEOz-SWCNT was below 0.4 mg/mL. The biocompatibility of PEOz-SWCNT on Hela cells was good, and the PTX@PEOz-SWCNT could significantly enhance the cell growth inhibition rate on MCF-7 cells. The in vitro antitumor activity test results showed that the cell uptake of the C6@PEOz-SWCNT was increased compared to C6@SWCNT. Conclusion PTX@PEOz-SWCNT drug delivery system is promising in tumor-targeted drug delivery.