National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People's Republic of China.
College of Biomedical Engineering, Sichuan University, Chengdu, 610064, People's Republic of China.
Int J Nanomedicine. 2022 Aug 25;17:3691-3710. doi: 10.2147/IJN.S375950. eCollection 2022.
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.
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.
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.
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 Ca 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).
The current study provides an effective strategy for OS therapy where the effectiveness was associated with the particle morphology and cell line.
近年来，利用羟基磷灰石纳米粒子（HANPs）进行肿瘤治疗引起了越来越多的关注，因为研究发现 HANPs 选择性地抑制肿瘤细胞的生长，但对正常细胞表现出可忽略的毒性。
本研究旨在探讨不同形态和粒径的 HANPs 对两种骨肉瘤（OS）细胞，人骨肉瘤 143B 细胞和大鼠骨肉瘤 UMR106 细胞的作用。
通过湿化学法制备了六种不同形态和粒径的 HANPs。然后，通过体外细胞实验和体内荷瘤小鼠模型来表征这些纳米粒子的抗肿瘤作用。还通过分析细胞内钙、凋亡相关基因的表达、活性氧（ROS）和粒子在肿瘤细胞中的内吞效率，研究了涉及线粒体凋亡的抗肿瘤机制。
体外细胞实验和体内小鼠模型评价均表明，HANPs 的抗 OS 性能取决于纳米粒子的浓度、形态和粒径以及 OS 细胞系。在六种 HANPs 中，棒状 HANPs（R-HANPs）对 143B 细胞的抑制活性最强，而针状 HANPs（N-HANPs）对 UMR106 细胞的生长抑制作用最强。我们进一步证明，HANPs 通过选择性地提高细胞内 Ca 和线粒体凋亡相关分子的基因表达水平，以及使肿瘤细胞的线粒体膜电位去极化，从而诱导线粒体凋亡，但在小鼠前成骨细胞系 MC3T3-E1 中则不会。此外，HANPs 的抗 OS 活性还与肿瘤细胞中粒子的内吞效率以及它们诱导氧化损伤和免疫原性细胞死亡（ICD）的能力有关。
本研究为 OS 治疗提供了一种有效的策略，其疗效与颗粒形态和细胞系有关。
