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载紫杉醇的银纳米粒子通过 ROS 介导的信号通路诱导 A549 细胞凋亡的功能化。

Functionalization of Silver Nanoparticles Loaded with Paclitaxel-induced A549 Cells Apoptosis Through ROS-Mediated Signaling Pathways.

机构信息

Guangzhou Chest Hospital, Guangzhou, China.

Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China.

出版信息

Curr Top Med Chem. 2020;20(2):89-98. doi: 10.2174/1568026619666191019102219.

Abstract

BACKGROUND

Paclitaxel (PTX) is one of the most important and effective anticancer drugs for the treatment of human cancer. However, its low solubility and severe adverse effects limited clinical use. To overcome this limitation, nanotechnology has been used to overcome tumors due to its excellent antimicrobial activity.

OBJECTIVE

This study was to demonstrate the anticancer properties of functionalization silver nanoparti- cles loaded with paclitaxel (Ag@PTX) induced A549 cells apoptosis through ROS-mediated signaling pathways.

METHODS

The Ag@PTX nanoparticles were charged with a zeta potential of about -17 mv and charac- terized around 2 nm with a narrow size distribution.

RESULTS

Ag@PTX significantly decreased the viability of A549 cells and possessed selectivity between cancer and normal cells. Ag@PTX induced A549 cells apoptosis was confirmed by nuclear condensation, DNA fragmentation, and activation of caspase-3. Furthermore, Ag@PTX enhanced the anti-cancer activity of A549 cells through ROS-mediated p53 and AKT signalling pathways. Finally, in a xenograft nude mice model, Ag@PTX suppressed the growth of tumors.

CONCLUSION

Our findings suggest that Ag@PTX may be a candidate as a chemopreventive agent and could be a highly efficient way to achieve anticancer synergism for human cancers.

摘要

背景

紫杉醇(PTX)是治疗人类癌症最有效和最重要的抗癌药物之一。然而,其溶解度低和严重的不良反应限制了其临床应用。为了克服这一限制,纳米技术因其优异的抗菌活性而被用于克服肿瘤。

目的

本研究旨在通过 ROS 介导的信号通路证明载紫杉醇的功能化银纳米粒子(Ag@PTX)对 A549 细胞凋亡的抗癌特性。

方法

Ag@PTX 纳米粒子带约-17 mV 的 ζ 电位,并具有约 2nm 的窄粒径分布。

结果

Ag@PTX 显著降低了 A549 细胞的活力,并具有在癌细胞和正常细胞之间的选择性。Ag@PTX 通过核浓缩、DNA 片段化和 caspase-3 的激活来诱导 A549 细胞凋亡。此外,Ag@PTX 通过 ROS 介导的 p53 和 AKT 信号通路增强了 A549 细胞的抗癌活性。最后,在异种移植裸鼠模型中,Ag@PTX 抑制了肿瘤的生长。

结论

我们的研究结果表明,Ag@PTX 可能是一种化学预防剂的候选药物,并且可能是实现人类癌症抗癌协同作用的一种高效方法。

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