Magnetic Hyperthermia via Zn0.2Mn0.8Fe2O4 Oleic Acid Nanoparticles Enhances Chemotherapy Efficacy in a Lewis Lung Carcinoma Model
TL;DR
The potential of MHT as a chemosensitizing approach that improves the efficacy and tolerability of cisplatin therapy is confirmed, although MHT without chemotherapy did not provide sustained inhibition of tumor growth or a significant increase in survival.
Abstract
Background/Objectives: Combining chemotherapy with local magnetic hyperthermia (MHT) is promising because heating tumor tissue can increase cell damage, sensitize cells to cytostatic drugs, impair DNA repair, and change tumor microenvironment permeability. This creates conditions for enhancing the antitumor efficacy of chemotherapy while potentially reducing systemic toxicity. The aim of this study was to evaluate the efficacy of MHT with Zn0.2Mn0.8Fe2O4@OA nanoparticles alone and in combination with cisplatin in a Lewis lung carcinoma model. Methods: Four types of magnetic nanoparticles were synthesized and characterized: Fe3O4 and Zn0.2Mn0.8Fe2O4 coated with oleic acid (OA) or SiO2-NH2. Their physicochemical and magnetothermal properties, cytotoxicity, reactive oxygen species generation, and biodegradation in vivo were evaluated. Antitumor efficacy was studied in C57Bl/6 mice with LLC tumors after intratumoral administration of nanoparticles and two MHT sessions (100 kHz, 8 kA/m, 30 min). In combination therapy, ZnMn@OA and cisplatin at doses of 9 or 18 mg/kg were used. Results/Conclusions: Zn0.2Mn0.8Fe2O4@OA combined efficient heating, biodegradation, and the most pronounced effect among the MHT-alone groups, although MHT without chemotherapy did not provide sustained inhibition of tumor growth or a significant increase in survival. The combination of Zn0.2Mn0.8Fe2O4@OA-MHT with cisplatin 9 mg/kg produced the best therapeutic outcome: median survival increased significantly by two fold compared with the control group and by 1.8-fold compared with the chemotherapy-alone group at the comparable cisplatin dose. This regimen also stabilized body weight, reduced systemic toxicity, and restored RBC, HGB, and HCT parameters to the level of healthy animals by day 7 of the experiment. These data confirm the potential of MHT as a chemosensitizing approach that improves the efficacy and tolerability of cisplatin therapy.