Peixoto Raphael Cândido Apolinário, Miranda-Vilela Ana Luisa, de Souza Filho José, Carneiro Marcella Lemos' Brettas, Oliveira Ricardo G S, da Silva Matheus Oliveira, de Souza Aparecido R, Báo Sônia Nair
Institute of Biological Sciences, Department of Cell Biology, University of Brasília (UnB), Brasilia, 70919-970, Brazil.
Tumour Biol. 2015 May;36(5):3325-36. doi: 10.1007/s13277-014-2966-x. Epub 2014 Dec 21.
Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.
乳腺癌是女性中最常见的癌症类型之一。使用磁性流体进行药物的特异性递送是一种有吸引力的化疗平台。在我们之前的研究中，已证明用柠檬酸铑（II）包覆的磁赤铁矿纳米颗粒（Magh-Rh2Cit）在体外具有细胞毒性，在体内具有抗肿瘤活性，随后在乳腺癌细胞中进行瘤内给药。在本研究中，我们的目的是采用静脉注射治疗，以评估这些制剂对携带原位4T1乳腺癌的Balb/c小鼠的全身抗肿瘤活性和毒性。通过分析血常规、血清丙氨酸转氨酶、铁和肌酐水平以及肝脏、肾脏和肺的组织学，评估雌性Balb/c小鼠静脉注射治疗的毒性。作为对照，通过肿瘤体积缩小、组织学和形态计量分析，评估柠檬酸铑（II）（Rh2Cit）、Magh-Rh2Cit和柠檬酸包覆的磁赤铁矿纳米颗粒（Magh-Cit）的抗肿瘤活性。Magh-Rh2Cit和Magh-Cit使肿瘤面积显著减小，且各实验组均未出现血液毒性作用或血清ALT和肌酐水平升高。小鼠肝脏和肾脏的组织病理学检查证实了这一观察结果。此外，在肺组织中证实了纳米颗粒的存在，且无形态学变化，这支持了我们的纳米制剂未诱导毒性作用的观点。尚未开展关于负载柠檬酸铑（II）的磁赤铁矿纳米颗粒全身作用的研究，因此本报告是探索这些化合物治疗乳腺癌的治疗潜力的合适起点。
