TREATMENT OF EHRLICH-SOLID-TUMOR-BEARING MICE BY MAGNETOHYPERTHERMIA: EFFICACY OF CITRATE-COATED MAGNETIC NANOPARTICLES SUBMITTED TO TWO DIFFERENT TYPES OF ALTERNATED (AC) MAGNETIC FIELD EQUIPMENT

Wanessa Pedroso Neves, Cesar Romero S. Sousa, Ana Luisa Miranda-Vilela, João Paulo Longo, Giseli L. S. Santos, Paulo E. N. de Souza, Zulmira G. M. Lacava

 

Institution: Faculty of Medicine, Faciplac, Campus Gama, Brazil

Objectives: As magnetohyperthermia emerges as a promising alternative to minimize the acute and chronic adverse effects of classical cancer treatments, this work aimed to evaluate the efficacy of a citrate-functionalized magnetic fluid (NPCit) sample in mediating magnetohyperthermia, using two types of equipment generating an AC magnetic field: a portable aparatus developed by our research group (CMagMHG) and a commercial one (Magnetherm, NanoTherics Ltd, Newcastle, United Kingdom), to treat Ehrlich solid breast tumor ectopically inoculated in female Swiss mice. Methodology: Animals intraperitoneally anesthetized with ketamine (80 mg/kg) and xylazine (10 mg/Kg) were subcutaneously inoculated with Ehrlich ascitic tumor cell suspension (2.575 × 107 viable cells) in the upper region of the head for solid form implantation. After 48 hours, mice received the following treatments: (a) filtered water and no tumor implantation (negative control; N=2); (b) tumor inoculation and no treatment (tumor control; N=2); (c) intratumoral injection of NPCit (40 ?L) containing 18 × 1018 particles/mL and exposure for 13 minutes to CMagMHG, operating at 1MHz with 40 Oe field amplitude (N=3); (d) intratumoral injection of NPCit and exposure for 13 minutes to Magnetherm, assembled with 17-turn coil, capacitive box B22, operating under 330 kHz, 4.9 A, 25 V and maximum field strength of 170 Oe (N=3). Treatments were performed once a day for three consecutive days. The tumor’s histopathology and semi-quantitative analysis of necrosis area were used to assess its aggressiveness and regression. Possible acute side effects were assessed by animals’ body and spleen weight and hemogram. Results: NPcit showed adequate biocompatibility and was effective in mediating magnetohyperthermia, which promoted non-significant reductions in tumor volume but significant increases in necrosis area using both types of equipment. Conclusion: Our findings evidence potential use of NPcit mediating magnetohyperthermia for future use as an adjuvant in breast cancer therapy.