Dextran-functionalized magnetic fluid mediating magnetohyperthermia for treatment of Ehrlich-solid-tumor-bearing mice: toxicological and histopathological evaluations

Abstract

Dextran-functionalized maghemite fluid (DexMF) has been tested to treat Ehrlich-solid-tumor-bearing mice, evidencing its potential use in mediating magnetohyperthermia in breast cancer treatment. However, although magnetic nanoparticles tend to accumulate in tumor tissues, part of the nanomaterial can reach the blood stream, and then the organism. The aim of this study was to investigate the acute systemic effects of the intratumoral injection of DexMF mediating magnetohyperthermia in the treatment of an advanced clinical Ehrlich-solid-tumor, assessed through histopathological analyses of liver, kidneys, heart and spleen, comet assay, micronucleus test, hemogram, and serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatinine, and urea. The tumor's histopathology and morphometry were used to assess its aggressiveness and regression. DexMF mediating hyperthermia was effective in containing tumor aggressiveness and in inducing tumor regression, besides showing no toxic effects. Its physical characteristics also suggest that it is safe to use in other biomedical applications.

Comparative Efficacy of a Biocompatible Citrate-Functionalized Magnetic Fluid Mediating Radiofrequency Hyperthermia and Magnetohyperthermia to Treat Ectopic Ehrlich-Solid-Tumor-Bearing Elderly Mice

“…Surface-functionalized superparamagnetic iron oxide nanoparticles (SPIONs) are usually based on magnetite (Fe 3 O 4 ) or maghemite (γ-Fe 2 O 3 ) nanoparticles [15,17,44,45], and represent a promising platform to build complex magnetic systems used for in vivo applications [35,46]. Since particle size and surface charge are important factors that determine their pharmacokinetics, toxicity and biodistribution [35,47], they must have adequate magnetic characteristics besides control in size and surface composition [43], because their physical characteristics can affect their in vivo performance [35,47]. size <10 nm to 20 nm exhibit an inimitable form of magnetism, i.e.…”

“…For this, the sample was dehydrated in a low vacuum environment and stored as a powder without atmospheric contact; using a Zetasizer (Zetasizer Nano-ZS90 Malvern Instruments Limited, Malvern, UK) we determined the hydrodynamic radius, the polydispersion index and its surface charge by dynamic light scattering (DLS) with the sample diluted in ultra-pure deionized water (1: 100), and the measurements were performed in triplicate at 25°C, with a fixed detection angle of 173°C; the physical mean diameter and its dispersion was determined by transmission electron microscopy (TEM) performed on a JEOL 1011 (JEOL USA, Inc.) with sample diluted in ultra-pure deionized water (1:500), deposited in a 300 mesh copper TEM grid supported by films of Formvar, dried at room temperature for 24 hours and then counterstained for 45 minutes with 1% Osmium (OsO 4 ) vapor. The average diameter of the sample evaluated by MET implantation [15,32,35,36]. Following 48 hours after xenograft, all mice had clinical tumor and received the following treatments: (a) filtered water and non-tumor-bearing mice (negative control); (b) xenograft and no treatment (tumor control); (c) intratumoral injection of NPCit (40 µL) containing 18 × 10 18 particles/mL and exposure for 13 minutes to CMagMHG; (d) intratumoral injection of NPCit and exposure for 13 minutes to Magnetherm.…”

“…Following 48 hours after xenograft, all mice had clinical tumor and received the following treatments: (a) filtered water and non-tumor-bearing mice (negative control); (b) xenograft and no treatment (tumor control); (c) intratumoral injection of NPCit (40 µL) containing 18 × 10 18 particles/mL and exposure for 13 minutes to CMagMHG; (d) intratumoral injection of NPCit and exposure for 13 minutes to Magnetherm. Treatments were performed once a day for three consecutive days [15,19,35]. Body weights were measured at the beginning and end of the treatment, and the animals were monitored for signs of toxicity such as weight loss, diarrhea, skin ulcers and deaths.…”

“…The cytotoxicity of NPs depends, among other things, on surface charge; NPs with positive charges are more toxic than negatively charged particles [35,50]. NPs with zeta potentials greater than +30 mV or less than -30 mV are considered strongly cationic and anionic, respectively, while those with a zeta potential between -10 and +10 mV are considered approximately neutral.…”

Preparation, Biodistribution of 99mTc-Azacytidine Complex as a Potential Agent for Radiotherapy

“…Ehrlich carcinoma is the correspondent of murine mammary adenocarcinoma. It has been chosen as a tumour model for this biodistribution study due to its ease of transplantation, aggressiveness and rapid growth 28,29 . As mentioned earlier, the purpose of the radiolabeling of 5-Aza with 99m Tc was to study the possibility of its future radiolabeling with 188/186 Re for radiotherapeutic use.…”