载多柔比星的 Pluronic P123 修饰纳米胶束增强了耐药乳腺癌细胞的肿瘤抑制作用。
Pluronic P123 modified nano micelles loaded with doxorubicin enhanced tumor-suppressing effect on drug-resistant breast cancer cells.
机构信息
Department of Thyroid and Breast III, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.
Department of Radiology, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei Province, China.
出版信息
Aging (Albany NY). 2020 May 12;12(9):8289-8300. doi: 10.18632/aging.103138.
OBJECTIVE
Nano micelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. This study aimed to investigated the anti-tumor effect of doxorubicin (Dox)-loaded Pluronic P123 (P123) and PEG2000-DSPE mixed NMs in drug-resistant breast cancer cells.
RESULTS
The expression of P-gp and MDR1 gene was highly expressed in MCF-7R but not MCF-7 cells. The cellular uptake of P123-PEG2000-DSPE (Dox) was higher than that of free Dox and PEG2000-DSPE (Dox) in MCF-7R cells. Furthermore, compared with free Dox, both PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) significantly diminished cell viability, and promoted cell apoptosis in MCF-7R cells. In addition, the P123-modified NMs obviously inhibited the expression of P-gp and MDR1.
CONCLUSIONS
P123-PEG2000-DSPE (Dox) had a superior anti-tumor activity than PEG2000-DSPE (Dox) in MCF-7R cells through P-gp-mediated drug excretion and drug resistance mechanisms.
METHODS
The PEG2000-DSPE NMs (PEG2000-DSPE), P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE), Dox-loaded PEG2000-DSPE NMs (PEG2000-DSPE (Dox)), and Dox-loaded Pluronic P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE (Dox)) were prepared, and then the morphologies and the size distribution of PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively.
目的
纳米胶束（NMs）由于其独特的物理化学性质，已广泛应用于各种生物医学应用。本研究旨在探讨载多柔比星（Dox）的 Pluronic P123（P123）和 PEG2000-DSPE 混合胶束（NMs）在耐药乳腺癌细胞中的抗肿瘤作用。
结果
MCF-7R 细胞中 P-糖蛋白（P-gp）和多药耐药基因 1（MDR1）的表达高度上调，但 MCF-7 细胞中则没有。与游离 Dox 和 PEG2000-DSPE（Dox）相比，MCF-7R 细胞中 P123-PEG2000-DSPE（Dox）的细胞摄取量更高。此外，与游离 Dox 相比，PEG2000-DSPE（Dox）和 P123-PEG2000-DSPE（Dox）均显著降低 MCF-7R 细胞活力，并促进细胞凋亡。此外，P123 修饰的纳米粒明显抑制 P-gp 和 MDR1 的表达。
结论
通过 P-gp 介导的药物外排和耐药机制，P123-PEG2000-DSPE（Dox）在 MCF-7R 细胞中的抗肿瘤活性优于 PEG2000-DSPE（Dox）。
方法
制备 PEG2000-DSPE 纳米粒（PEG2000-DSPE）、P123 和 PEG2000-DSPE 混合纳米粒（P123-PEG2000-DSPE）、载多柔比星的 PEG2000-DSPE 纳米粒（PEG2000-DSPE（Dox））和载 Pluronic P123 和 PEG2000-DSPE 混合纳米粒（P123-PEG2000-DSPE（Dox）），然后分别通过透射电子显微镜（TEM）和动态光散射（DLS）观察 PEG2000-DSPE（Dox）和 P123-PEG2000-DSPE（Dox）的形态和粒径分布。
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