がんの科学と治療

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

Abstract

Wanessa Pedroso Neves, Cesar Romero Soares Sousa1, Ana Luisa Miranda-Vilela1, Gisele Lorranna Silva Santos, Paulo Eduardo N de Souza, João Paulo Figueiró Longo, and Zulmira Guerrero Marques Lacava

Objective: We aimed to evaluate the efficacy of a biocompatible citrate-functionalized magnetic fluid (NPCit) sample in mediating hyperthermia, using two types of alternated (AC) magnetic field equipment operating in two different ways: a portable apparatus, generating an electromagnetic field in MHz range (radiofrequency range; radiofrequency hyperthermia-RFHT) developed by our research group (CMagMHG), and a commercial one working in kHz range (magnetohyperthermia-MHT) (Magnetherm, NanoTherics Ltd, Newcastle, United Kingdom), to treat ectopic Ehrlich-solid-tumor-bearing elderly mice.

Methods: Females intraperitoneally anesthetized with ketamine (80 mg/kg) and xylazine (10 mg/Kg) were subcutaneously inoculated with Ehrlich ascitic tumor cell suspension (1.03 × 106 viable cells) in the upper head region for solid form implantation. After 48 hours, mice received one of four treatments: (a) filtered water and no tumor implantation (negative control); (b) tumor inoculation and no treatment (tumor control); (c) intratumoral injection of NPCit (40 µL) containing 18 × 1018 particles/mL and 13 minutes’ exposure to CMagMHG, operating at 1MHz, 40 Oe field amplitude; (d) intratumoral injection of NPCit and 13 minutes’ exposure to Magnetherm, assembled with 17-turn coil, capacitive box B22, operating under 330 kHz, 4.9 A, 25 V and maximum field strength 170 Oe. Treatments occurred once daily for three consecutive days. Tumor histopathology and semi-quantitative analysis of necrosis area served to assess tumor 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 RFHT and MHT, which promoted significant increases in necrosis area using both equipment types.

Conclusion: Our findings evidence the potential use of NPcit mediating hyperthermia for future use as an adjuvant in breast cancer therapy.