负载紫杉醇双配体纳米药物输送系统的体外生物性能评价

摘要

Objective To evaluate in vitro biological activities of paclitaxel nanoparticles with dual ligands. Meth-ods The cells were incubated with H-F-P NPs,H-Tat-P NPs,or H-F-Tat-P NPs,and then evaluated by using flow cytometry. Then the cells were incubated with H-F-Tat-P NPs,and evaluated by using confocal laser scanning microscopy. Results Quantitative analysis of cellular uptake of NPs by flow cytometry showed the extend of celluar uptake for A549 cell lines was:H-F-Tat-P NPs > H-Tat-P NPs > H-F-P NPs. For MDA-MB-231 cells:H-F-Tat-P NPs >H-F-P NPs> H-Tat-P NPs. Quali-tative analysis of cellular uptake of H-F-Tat-P NPs by confocal laser scanning microscopy showed the fluorescent signal of NPs in MDA-MB-231 cells was higher than that of A549 cells under the same conditions. Conclusion The strategy on nano-medicine with dual ligands can enhance the cellular uptake of drug thereby improve its chemotherapeutic efficiency. The nano-particle system could be used as a promising cancer cell specific delivery system for further investigation.%目的：体外评价带有叶酸和穿膜肽双配体的、负载紫杉醇纳米药物输送系统的生物性能。方法分别用H-F-P NPs、H-Tat-P NPs及H-F-Tat-P NPs孵育细胞，利用流式细胞仪定量评价细胞对带有不同配体纳米药物输送系统的摄取量。再用H-F-Tat-P NPs孵育细胞，利用激光共聚焦显微镜定性评价不同细胞对H-F-Tat-P NPs的摄取量。结果叶酸受体阳性表达的MDA-MB-231细胞摄取H-F-Tat-P NPs的量明显多于H-F-P NPs及H-Tat-P NPs。叶酸受体阴性表达的A549细胞摄取H-F-Tat-P NPs与H-Tat-P NPs的量多于H-F-P NPs。结论叶酸的靶向作用与穿膜肽的穿膜作用能够协同提高药物在靶细胞的聚集，进一步增强药物输送系统的治疗作用，为开发新型、高效药物输送系统提供基础。