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

Journal of Nanobiotechnology

Research

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

[1] Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília (UnB), 70.910-900, Brasília-DF, Brazil;Departamento de Patologia, Faculdade de Medicina, Universidade de Brasília, 70.919-970, Brasília-DF, Brazil;Faculdade LS, 72.020-111, Brasília-DF, Brazil;Instituto de Química, Universidade Federal de Goiás, Campus Samambaia, 74.001-970, Goiânia, Brazil;

关键词: Rhodium;    Maghemite;    Magnetic Fluid;    Superparamagnetic Iron Oxide Nanoparticles;    Maghemite Nanoparticles;   

DOI  :  10.1186/1477-3155-11-4

 received in 2012-10-02, accepted in 2013-01-30,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMagnetic 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.MethodsMice 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.ResultsRegarding 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.ConclusionsIn 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.

【 授权许可】

CC BY   
© Carneiro et al; licensee BioMed Central Ltd. 2013