Open Access Research

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

Marcella Lemos Brettas Carneiro1*, Raphael CA Peixoto1, Graziela A Joanitti1, Ricardo GS Oliveira1, Luis AM Telles1, Ana L Miranda-Vilela1, Anamélia L Bocca1, Leonora MS Vianna2, Izabel CR da Silva3, Aparecido R de Souza4, Zulmira GM Lacava1 and Sônia N Báo1

Author Affiliations

1 Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília (UnB), 70.910-900, Brasília-DF, Brazil

2 Departamento de Patologia, Faculdade de Medicina, Universidade de Brasília, 70.919-970, Brasília-DF, Brazil

3 Faculdade LS, 72.020-111, Brasília-DF, Brazil

4 Instituto de Química, Universidade Federal de Goiás, Campus Samambaia, 74.001-970, Goiânia, Brazil

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Journal of Nanobiotechnology 2013, 11:4  doi:10.1186/1477-3155-11-4

Published: 16 February 2013

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.