细胞穿膜-靶向双肽修饰紫杉醇纳米制剂的制备、表征及体外抗胶质瘤评价

目的 以胶质瘤U251细胞为研究对象,制备细胞穿膜-靶向双肽修饰的紫杉醇纳米制剂(TN-PTX),研究其性质及体外抗肿瘤活性。 方法 采用噬菌体展示技术体外筛选与U251细胞特异性结合的靶向肽;界面沉淀法制备紫杉醇(PTX)纳米粒,将靶向肽、细胞穿膜肽TAT修饰于其表面,制备TN-PTX;对TN-PTX的粒径、Zeta电位、载药量、形态外貌、体外释放等方面进行表征; CCK8实验探讨TN-PTX对U251细胞增殖能力的影响。 结果 筛选的靶向肽HK特异性良好,TN-PTX的粒径为350.5±31.8nm,Zeta电位为-31.9±5.0mV,载药量为5.01%,形貌基本呈圆球形,分布较均匀,体外释放缓慢。PTX浓度相同时,TN-PTX对U251细胞的杀伤作用比PTX强。 结论 TN-PTX性质稳定,具有一定缓释作用,在细胞水平对U251细胞具有更强的细胞毒性作用。

Preparation, Characteristics and Anti-tumoral Efficacy in vitro of Cell Penetrating Peptide Modified Paclitaxel Targeted Nanoparticles

Objective In order to prepare cell penetrating peptide modified paclitaxel PLGA targeted nanoparticles (TN-PTX), and evaluate the properties and the anti-tumoral efficacy of the nanoparticles in vitro. Methods The targeting peptide was specifically screened in human glioma U251 cells by phage display technology and paclitaxel (PTX) nanoparticels were prepared by the interfacial precipitation method. We successfully prepared a novel paclitaxel targeted nanoparticles modified with the targeting peptide and the cell penetrating peptide TAT by amide condensation reaction. Characteristics of TN-PTX, including particle size, Zeta potential, drug loadings, the morphological appearance, were investigated and the anti-tumoral efficacy of TN-PTX was also evaluated in vitro. Results The targeting peptide exhibited a good specificity to glioma. The particle size of TN-PTX was 350.5±31.8nm, and the Zeta potential was-31.9±5.0mV, and drug loading was 5.01%. The morphology of TN-PTX is basically homogeneous sphere. In vitro inhibition study results indicated that TN-PTX exhibited more efficient inhibitory effects on the U251 cells than PTX with the same concentration of PTX. Conclusion TN-PTX possessed the stable properties and significantly inhibited the tumor proliferation than PTX in vitro.