Laboratory of Immunology and Virology, Faculty of Biological Sciences, Autonomous University of Nuevo Leon, Monterrey, Mexico.
Int J Nanomedicine. 2018 May 31;13:3235-3250. doi: 10.2147/IJN.S165289. eCollection 2018.
Nanotechnology has gained important interest, especially in the development of new therapies; the application of gold nanoparticles (AuNPs) in the treatment and detection of diseases is a growing trend in this field. As cancer represents a serious health problem around the world, AuNPs are studied as potential drugs or drug carriers for anticancer agents. Recent studies show that AuNPs stabilized with chitosan (CH) possess interesting biological activities, including potential antitumor effects that could be selective to cancer cells.
In this study, we synthesized sodium citrate-AuNPs and CH-capped AuNPs of 3-10 nm, and analyzed their cytotoxicity in cervical (HeLa) and breast (MCF-7) cancer cells, and in peripheral blood mononuclear cells (PBMCs). Then, we evaluated the clonogenic potential, cell cycle, nuclear alterations, caspase dependence, and reactive oxygen species (ROS) production in HeLa and MCF-7 cells after chitosan gold nanoparticles (CH-AuNPs) exposure.
Our data showed that CH-AuNPs are cytotoxic in a dose-dependent manner in the cancer cell lines tested, while they induce low cytotoxicity in PBMCs. Sodium citrate gold nanoparticles did not show cytotoxic effects. In both HeLa and MCF-7 cell lines, CH-AuNPs inhibit clonogenic potential without inducing cell cycle arrest or nuclear alterations. The cell death mechanism is specific for the type of cancer cell line tested, as it depends on caspase activation in HeLa cells, whereas it is caspase independent in MCF-7 cells. In all cases, ROS production is mandatory for cell death induction by CH-AuNPs, as ROS inhibition with N-acetyl cysteine inhibits cell death.
Our results show that CH-AuNPs are selective for HeLa and MCF-7 cancer cells, rather than normal PBMCs, and that ROS production seems to be a conserved feature of the cell death mechanism induced by CH-AuNPs. These results improve the knowledge of CH-AuNPs and open the way to the design of new pharmacological strategies using these agents against cancer.
纳米技术引起了人们的浓厚兴趣，尤其是在新疗法的开发方面；金纳米粒子（AuNPs）在疾病的治疗和检测中的应用是该领域的一个新兴趋势。由于癌症是全球严重的健康问题，AuNPs 被研究为抗癌药物或药物载体的潜在药物。最近的研究表明，壳聚糖（CH）稳定的 AuNPs 具有有趣的生物活性，包括对癌细胞可能具有选择性的抗肿瘤作用。
在本研究中，我们合成了柠檬酸- AuNPs 和 CH 封端的 3-10nm AuNPs，并分析了它们在宫颈（HeLa）和乳腺癌（MCF-7）细胞以及外周血单核细胞（PBMCs）中的细胞毒性。然后，我们评估了壳聚糖金纳米粒子（CH-AuNPs）暴露后 HeLa 和 MCF-7 细胞的集落形成能力、细胞周期、核改变、半胱天冬酶依赖性和活性氧（ROS）产生。
我们的数据表明，CH-AuNPs 在测试的癌细胞系中以剂量依赖的方式表现出细胞毒性，而在 PBMCs 中诱导低细胞毒性。柠檬酸金纳米粒子没有表现出细胞毒性。在 HeLa 和 MCF-7 细胞系中，CH-AuNPs 抑制集落形成能力而不诱导细胞周期停滞或核改变。细胞死亡机制因所测试的癌细胞系类型而异，因为它依赖于 HeLa 细胞中的半胱天冬酶激活，而在 MCF-7 细胞中则不依赖于半胱天冬酶。在所有情况下，ROS 的产生对于 CH-AuNPs 诱导的细胞死亡是必需的，因为用 N-乙酰半胱氨酸抑制 ROS 产生会抑制细胞死亡。
我们的结果表明，CH-AuNPs 对 HeLa 和 MCF-7 癌细胞具有选择性，而对正常 PBMCs 则没有，并且 ROS 的产生似乎是 CH-AuNPs 诱导的细胞死亡机制的一个保守特征。这些结果提高了对 CH-AuNPs 的认识，并为利用这些药物针对癌症设计新的药理学策略开辟了道路。
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