A Selective Reduction of Osteosarcoma by Mitochondrial Apoptosis Using Hydroxyapatite Nanoparticles

利用羟基磷灰石纳米粒子选择性减少骨肉瘤的线粒体凋亡

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作者:Hongfeng Wu, Shuo Liu, Siyu Chen, Yuchen Hua, Xiangfeng Li, Qin Zeng, Yong Zhou, Xiao Yang, Xiangdong Zhu, Chongqi Tu, Xingdong Zhang

Background

In recent years, using hydroxyapatite nanoparticles (HANPs) for tumor therapy attracted increasing attention because HANPs were found to selectively suppress the growth of tumor cells but exhibit ignorable toxicity to normal cells.

Conclusion

The current study provides an effective strategy for OS therapy where the effectiveness was associated with the particle morphology and cell line.

Methods

Six kinds of HANPs with different morphologies and particle sizes were prepared by wet chemical method. Then, the antitumor effect of these nanoparticles was characterized by means of in vitro cell experiments and in vivo tumor-bearing mice model. The underlying antitumor mechanism involving mitochondrial apoptosis was also investigated by analysis of intracellular calcium, expression of apoptosis-related genes, reactive oxygen species (ROS), and the endocytosis efficiency of the particles in tumor cells.

Purpose

This study aimed to investigate the capacities of HANPs with different morphologies and particle sizes against two kinds of osteosarcoma (OS) cells, human OS 143B cells and rat OS UMR106 cells.

Results

Both in vitro cell experiments and in vivo mice model evaluation revealed the anti-OS performance of HANPs depended on the concentration, morphology, and particle size of the nanoparticles, as well as the OS cell lines. Among the six HANPs, rod-like HANPs (R-HANPs) showed the best inhibitory activity on 143B cells, while needle-like HANPs (N-HANPs) inhibited the growth of UMR106 cells most efficiently. We further demonstrated that HANPs induced mitochondrial apoptosis by selectively raising intracellular Ca2+ and the gene expression levels of mitochondrial apoptosis-related molecules, and depolarizing mitochondrial membrane potential in tumor cells but not in MC3T3-E1, a mouse pre-osteoblast line. Additionally, the anti-OS activity of HANPs also linked with the endocytosis efficiency of the particles in the tumor cells, and their ability to drive oxidative damage and immunogenic cell death (ICD).

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