Jin Shi-hua, Li Ning-chen, Zhang Zhi-hong, Na Yan-qun
Shougang Hospital & Wujieping Urology Center of Peking University, Beijing 100144, China.
Zhonghua Yi Xue Za Zhi. 2012 Nov 27;92(44):3151-4.
To evaluate the effects of modification of transferrin on cytotoxicity and intracellular delivery of paclitaxel loaded Poly (lactide-co-glycolide) (PLGA) nanoparticle (NPs).
PLGA NPs were formulated with microemulsion method, Polyvinyl alcohol (PVA) was used as surfactant (PVA NPs). Transferrin (Tf) was used to modify the NPs (Tf NPs). The cytotoxicity of paclitaxel solution and paclitaxel loaded PVA NPs and Tf NPs were measured in bladder cancer cell line J-82. The intracellular delivery of two kinds of NPs was measured.
The half maximal inhibitory concentration (IC50) of paclitaxel loaded PVA NPs and Tf NPs was (44 ± 7) and (49 ± 11) ng/ml respectively and significantly lower than that of paclitaxel solution, which was (81 ± 18) ng/ml (both P < 0.05). The uptake of PVA NPs and Tf NPs by J-82 cells after 2 hours was (89 ± 19) µg/mg cellular protein and (76 ± 16) µg/mg cellular protein. The uptake of two kinds of NPs had no significantly difference. The intracellular level of NPs decreased significantly upon the withdrawal of NPs in medium. However, it became stable 2 hours later and 11.3% PVA NPs and 18.0% Tf NPs remained. The intracellular level of PVA NPs and Tf NPs had no significantly difference at any time point. NPs were distributed in cytoplasm after endocytosis.
PLGA NPs can significantly improve the anti-neoplastic effect of paclitaxel on bladder cancer. However, modification of Tf does not change the intracellular dynamics.
评估转铁蛋白修饰对负载紫杉醇的聚（丙交酯-共-乙交酯）（PLGA）纳米粒（NPs）细胞毒性及细胞内递送的影响。
采用微乳液法制备PLGA NPs，以聚乙烯醇（PVA）作为表面活性剂（PVA NPs）。用转铁蛋白（Tf）修饰NPs（Tf NPs）。在膀胱癌细胞系J-82中测定紫杉醇溶液、负载紫杉醇的PVA NPs和Tf NPs的细胞毒性。测定两种NPs的细胞内递送情况。
负载紫杉醇的PVA NPs和Tf NPs的半数最大抑制浓度（IC50）分别为（44±7）和（49±11）ng/ml，显著低于紫杉醇溶液的（81±18）ng/ml（均P<0.05）。J-82细胞在2小时后对PVA NPs和Tf NPs的摄取量分别为（89±19）μg/mg细胞蛋白和（76±16）μg/mg细胞蛋白。两种NPs的摄取量无显著差异。当培养基中撤去NPs后，细胞内NPs水平显著下降。然而，2小时后变得稳定，剩余11.3%的PVA NPs和18.0%的Tf NPs。在任何时间点，PVA NPs和Tf NPs的细胞内水平均无显著差异。NPs在胞吞作用后分布于细胞质中。
PLGA NPs可显著提高紫杉醇对膀胱癌的抗肿瘤作用。然而，Tf修饰并未改变细胞内动力学。
