Antitumor effect of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles on mice bearing breast cancer: a systemic toxicity assay

Abstract

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.

Formation of Protein Corona on Rhodium Citrate-Functionalized Magnetic Nanoparticles and Their Interaction with Human Macrophages

“…Otherwise, after the adsorption of ligands, the complexation of NPs' surface by carboxylic moieties of RhCit took place. Besides, some -COOH moieties remained solution-oriented, as free ionizable groups, providing the negative superficial charge and increasing the colloidal stability of Mag-RhCit NPs through electrostatic interparticle repulsion [7,23,24].…”

“…Previous studies with maghemite NPs and maghemite NPs functionalized with rhodium (II) citrate (Magh-RhCit) showed progress and great potential for chemotherapeutic treatment [7,[20][21][22][23][24]. However, as yet there are no studies related to the identification of the protein corona of this NP nor about its interaction in cells of the immune system.…”

The Patient with Multiple Endocrine Neoplasia Type 2B Treated with Citric Acid already Survived 8 Years Longer than Medically Expected

“…I have already reported 13 cases of patients with cancer who have improved impressively only with the citric acid treatment that they have received, considering that they are literally cured, including this patient with medullary thyroid cancer [1], patients with peritoneal mesothelioma [4] myeloid leukemia [5], Hürthle thyroid tumor [6], endocrine hepatic tumor [7], esophageal cancer [8], multiple myeloma [9], glioblastoma multiforme [10], pancreatic cancer [11] Non Hodgkin lymphoma [12] bladder cancer [13], breast cancer [14] and a patient with multiple myeloma remitted only in 10 days with the treatment of citric acid that she received [15]; also, the fact that citric acid [citrate] is effective as a cancer treatment is demonstrated in laboratory animals [16]; but this case reported in this article is very relevant, the survival rate of an endocrine neoplasia type 2B was overcome more than 8 years only with the treatment of citric acid that the patient received.…”

Comparison of the effect of rhodium citrate-associated iron oxide nanoparticles on metastatic and non-metastatic breast cancer cells

“…Current studies with maghemite nanoparticles, an iron oxide compound, have demonstrated in vitro and in vivo specific cytotoxic action for target cells, and these results have indicated this nanoparticle as a promising option for drug delivery (Manikandan et al 2018;Chaves et al 2017;Magro et al 2018). Maghemite nanoparticles associated with rhodium citrate (MRC) have showed colloidal stability and antitumor activity in breast cancer cells (Carneiro et al 2011;Peixoto et al 2015;Chaves et al 2015;da Silva Nunes et al 2013;Rocha et al 2017).…”