纳米医学与纳米技术杂志

抽象的

Rhodium Citrate Associated with Maghemite Nanoparticles Causes DNA Fragmentation Independently of Caspases 3 and Mediated by Reactive Oxygen Species

Natalia Lemos Chaves, Cláudio Afonso Pinho Lopes, Marcella Lemos Brettas Carneiro, Aparecido Ribeiro de Souza, Matheus Oliveira da Silva, José Raimundo Corrêa and Sônia Nair Báo

Breast cancer is the most common cancer among women, excluding non-melanoma skin cancer. Research efforts have been directed towards the development of more efficient drugs against this disease, such as metal complexes, which have been widely studied. These compounds can intercalate in DNA bases and impair DNA transcription and replication, leading to cell death. Cell death can also be associated with early induction of reactive oxygen species (ROS) production by cells treated with this kind of metal complex. Nevertheless, the use of these compounds is limited because of their systemic toxicity. In this regard, the use was proposed of dirhodium citrate [Rh2(H2cit)4] associated with magnetic nanoparticles (NPs), which are carriers that may work in decreasing systemic toxicity. We compared cell viability effects of free Rh2(H2cit)4, Rh2(H2cit)4-loaded maghemite NPs [Magh-Rh2(H2cit)4] and maghemite nanoparticles loaded with citrate (Magh-cit), on MCF-7 breast cancer cells and MCF-10A non-tumor and non-tumorigenic epithelial cells by MTT assay. Furthermore, we examined whether the NPs induce cell death by apoptosis in a cell line without caspase 3 expression (MCF-7). This feature was demonstrated by quantification of ROS through labeling cells with DCFDA, DNA fragmentation studies analyzed with a flow cytometer, release of cytochrome C from mitochondria assays, and effector caspases activation analysis (revealed by FLICA) as visualized by confocal microscopy. Our results confirmed that rhodium citrate was less cytotoxic in its free form than when associated with the tested drug delivery system. Moreover, Magh-Rh2(H2cit)4 NPs and Magh-cit NPs induced apoptosis cell death mediated by ROS and independently of caspase 3 expression.