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Title: Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer
Authors: Carneiro, Marcella Lemos Brettas
Peixoto, Raphael Cândido Apolinário
Joanitti, Graziella Anselmo
Oliveira, Ricardo GS
Telles, Luís Augusto Muniz
Miranda-Vilela, Ana Luisa
Bocca, Anamélia Lorenzetti
Vianna, Leonora Maciel de Souza
Silva, Izabel Cristina Rodrigues da
Souza, Aparecido R de
Lacava, Zulmira Guerrero Marques
Báo, Sônia Nair
Assunto:: Fluidos magnéticos
Issue Date: 2014
Publisher: Jornal de Nanobiotecnologia
Citation: CARNEIRO, Marcella Lemos Brettas, et al. Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer. Tumor Biology, v. online, p. 1-16, 2014. Disponível em: <>. Acesso em: 16 jan. 2015.
Abstract: Background: Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods: Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results: Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions: In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications.
Licença:: Este é um artigo Open Access distribuído sob os termos da Licença Creative Commons Attribution ( ), que permite o uso irrestrito, distribuição e reprodução em qualquer meio, desde que a obra original é devidamente citada. Fonte: Acesso em: 16 jan. 2015.
Appears in Collections:CEL - Artigos publicados em periódicos

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