Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy

Abstract

BackgroundRhodium (II) citrate (Rh2(H2cit)4) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh2(H2cit)4 as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh2(H2cit)4 and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh2(H2cit)4) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures.ResultsTreatment with free Rh2(H2cit)4 induced cytotoxicity that was dependent on dose, time, and cell line. The IC50 values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh2(H2cit)4-loaded maghemite nanoparticles (Magh-Rh2(H2cit)4) and Rh2(H2cit)4-loaded magnetoliposomes (Lip-Magh-Rh2(H2cit)4) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh2(H2cit)4, were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh2(H2cit)4 induces cell death by apoptosis.ConclusionsThe treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh2(H2cit)4 treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh2(H2cit)4 delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development.

Co-nanoencapsulation of magnetic nanoparticles and selol for breast tumor treatment: in vitro evaluation of cytotoxicity and magnetohyperthermia efficacy

“…Likewise, 10 to 100 nm are considered to be the ideal MNP diameters that avoid their recognition by the mononuclear phagocyte system, thus, allowing for a longer stay in the bloodstream, and promoting effective biodistribution. 3,29 In accordance with this desirable characteristic, maghemite nanoparticles used to prepare the magnetic nanocapsules evaluated in our study presented with a 10.0 nm (±2.5 nm) diameter, as observed by TEM micrograph. Further, the possibility of developing highly biocompatible polymericbased magnetic nanostructures using engineered maghemite nanoparticles 28 that are able to induce magnetohyperthermia was previously demonstrated.…”

“…23 The positive staining with annexin-V in cells is an indication of phosphatidylserine exposure in the plasma membrane, an event closely related to apoptosis. 3 A dose related increase was observed after 48 hours' treatment with MSE-NC (50 µg/mL of selol + 2.5 × 10 9 particles/mL (2X) and 200 µg/mL of selol + 1 × 10 10 particles/mL (8X)) while using breast cancer cells positively stained with annexin-V. Our findings are in very good agreement with the findings by Suchocki et al,20 which showed that the use of selol induced apoptosis in human leukemia cells. Apoptosis has been described as one of the more important mechanisms for the anticancer action of selenium-based compounds.…”

“…The size and the morphology of nanocapsules and nanosized magnetic particles were assessed by both transmission electron microscopy (TEM, JEOL 1011; JEOL Ltd, Tokyo, Japan) 3 and scanning electron microscopy (JEOL JSM-7001F; JEOL Ltd). TEM images were analyzed and the size distribution of nanocapsules and maghemite nanoparticles were obtained by counting at least 300 units using the Image Pro-Plus 5.1 software (Media Cybernetics, Inc, Rockville, MD).…”

“…3 First, 4T1 and MCF-7 cells were seeded into a 6-well culture plate at a density of 1.25 × 10 5 cells/mL, and allowed to attach to the plate for 24 hours. Subsequently, cells were treated with MSE-NC (2X = 50 µg/mL of selol + 2.5 × 10 9 particles/mL and 8X = 200 µg/mL of selol + 1 × 10 10 particles/mL), M-NC (2X = 2.5 × 10 9 particles/mL), SE-NC (2X = 50 µg/mL of selol), or paclitaxel (40 µg/mL).…”

“…[1][2][3] In general, DDS represent an important tool to improve the efficacy of drugs by increasing their bioavailability in the targeted area, thus enhancing the drug's solubility while decreasing undesirable side effects. 4,5 A number of nanomaterials, including polymeric nanostructures, magnetic nanoparticles (MNPs), liposomes, and dendrimers, are used as DDS.…”