CONICET- Universidad de Buenos Aires. Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN). Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Disfunción Celular en Enfermedades Neurodegenerativas y Nanomedicina. Ciudad Autónoma de Buenos Aires, Argentina.
Facultad de Ciencias Exactas, Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina.
Toxicol Sci. 2019 May 1;169(1):34-42. doi: 10.1093/toxsci/kfz019.
Hydroxyapatite (Ca10(PO4)6(OH)2; HAP) is an essential component of the human bone inorganic phase. At the nanoscale level, nano-HAP (nHAP) presents marked emergent properties differing substantially from those of the bulk counterpart. Interestingly, these properties depend on nanoparticle characteristics. In this study, we investigated the cytotoxicity of rod-shaped crystalline nHAP (10-20 nm × 50-100 nm) in both normal (ARPE-19, BV-2) and tumoral (HepG2, HEp-2, A549 and C6) cells. We found that nHAP was cytotoxic in tumor HEp-2, A549, and C6 cells. Moreover, it induced an expansion of the lysosomal compartment at sublethal concentrations in different cell lines, while lysosomal membrane damage was not detected. In C6 glioma cells, the most sensitive cell line to nHAP, these nanoparticles increased reactive oxygen species (ROS) production and induced DNA damage measured by γ-H2AX phosphorylation. Interestingly, our data also show for the first time that nHAP affects both cell unlimited proliferative capacity and cell migration, two of the major pathways involved in cancer progression. The present results showed the cytotoxic and antiproliferative effects of nHAP and suggest its potential as an alternative agent for glioma therapy.
羟基磷灰石(Ca10(PO4)6(OH)2;HAP)是人体骨骼无机相的重要组成部分。在纳米尺度上,纳米羟基磷灰石(nHAP)呈现出显著的突现性质,与体相物质有很大的不同。有趣的是,这些性质取决于纳米颗粒的特性。在这项研究中,我们研究了棒状结晶 nHAP(10-20nm×50-100nm)在正常(ARPE-19、BV-2)和肿瘤(HepG2、HEp-2、A549 和 C6)细胞中的细胞毒性。我们发现 nHAP 在肿瘤 HEp-2、A549 和 C6 细胞中具有细胞毒性。此外,它在不同细胞系中以亚致死浓度诱导溶酶体区室扩张,而未检测到溶酶体膜损伤。在 C6 神经胶质瘤细胞中,nHAP 对最敏感的细胞系,这些纳米颗粒增加了活性氧(ROS)的产生,并诱导γ-H2AX 磷酸化测量的 DNA 损伤。有趣的是,我们的数据还首次表明,nHAP 影响细胞无限制增殖能力和细胞迁移,这是癌症进展中涉及的两个主要途径。本研究结果表明 nHAP 具有细胞毒性和抗增殖作用,提示其可能成为治疗神经胶质瘤的一种替代药物。