Study on the therapeutic effect and some immune factors by methotrexate modified superparamagnetic nanoparticles in rat mammary tumors†

Abstract

Objective: this study investigates the efficacy, immunological impact, and preliminary safety of methotrexate (MTX) modified magnetic Fe₃O₄ nanoparticles in thermochemotherapy for mammary tumors in rats. Methods: transmission electron microscopy images revealed that the MTX-modified magnetic Fe₃O₄ nanoparticles are nearly spherical, approximately 10 nm in diameter. Chemically co-precipitated PEI-modified magnetic nanoparticles were utilized for thermotherapy, while MTX-modified nanoparticles were employed for thermochemotherapy. These nanoparticles were locally injected into the Walker-256 tumor tissues of Wistar rats. The experimental design included twelve groups, encompassing various protocols of thermotherapy and thermochemotherapy at 47 °C and 42 °C, a group receiving only MTX nanoparticle chemotherapy, and several control groups. The biodistribution of residual magnetic nanoparticles was assessed in vital organs such as the heart, liver, lungs, kidneys, and brain. Results: demonstrated that these magnetic nanoparticles primarily accumulated in the tumor's central region and were unevenly distributed at the margins. The nanoparticles were capable of penetrating tumor cells but were more dispersed around them. Importantly, no residual magnetic nanoparticles were detected in vital organs. Significant tumor reduction and prolonged survival times were observed in the 47 °C thermochemotherapy group, the 47 °C thermotherapy group and the repeated 42 °C thermochemotherapy group. Additionally, significant increases in IL-2 and IFN-γ levels, along with a decrease in IL-4 levels, were detected in the 47 °C thermochemotherapy and 47 °C thermotherapy groups. Conclusion: MTX-modified Fe₃O₄ magnetic nanoparticles demonstrate potential as an effective medium for thermochemotherapy. They are safe, tolerable, contribute to prolonged survival, and enhance immune functions in tumor-bearing rats without leaving residues in vital organs. These results provide a promising foundation for future cancer treatment research.