Abstract Despite the efforts of the medical and research community for effective treatments, cancer is one of the leading causes of death worldwide. Cancer cells’ enduring resistance is a significant cause of treatment failure. One of the most effective approaches proposed to overcome this resistance is a combination therapy. This is a transformative strategy by integrating complementary techniques such as radiation therapy, immunotherapy, photothermal treatment, photodynamic therapy, and hyperthermia, as well as combined with chemotherapy. Numerous studies have investigated the synergistic effects of these therapies to identify the most effective methods for cancer therapy. Researchers also found that magnetic nanoparticles can play a central and innovative role by enhancing the synergistic interactions of combination therapies. Their magnetic reactivity, high surface-to-volume ratio, and surface functionalization enable precise tumor-selective targeting, controlled drug delivery, and efficient conversion of light into heat. They can act as mediators, providing significant benefits when two or more therapeutic methods are used simultaneously. This can enhance their effectiveness. Mechanistically, magnetic nanoparticle-mediated hyperthermia enhances chemotherapy efficacy by elevating tumor temperatures, increasing membrane permeability, and promoting tumor sensitization to radiotherapy. The production of reactive oxygen species (ROS) in cancerous cells, the exacerbation of oxidative damage during photothermal therapy, and the enhancement of immune activation in combined immunotherapeutic approaches improve the effectiveness of chemotherapy. Biocompatible materials such as PEG, chitosan, and dextran can further stabilize these nanoparticles, and ligand functionalization enhances selective tracking of cancer cells. This article provides a comprehensive review of the multifunctional role of magnetic nanoparticles across diverse therapeutic combinations, including radiotherapy, immunotherapy, photothermal therapy, photodynamic therapy, and hyperthermia. It will help those interested in this research topic to comprehensively and validly compare and investigate various studies, make informed decisions, and introduce next-generation Magnetic nanoparticle-based combination therapies for cancer treatment.
Damavandi et al. (2026) studied this question.