Synergistic Effect of Ferroptosis‐Inducing Nanoparticles and X‐Ray Irradiation Combination Therapy

Abstract

Ferroptosis, characterized by the induction of cell death via lipid peroxidation, has been actively studied over the last few years and has shown the potential to improve the efficacy of cancer nanomedicine in an iron‐dependent manner. Radiation therapy, a common treatment method, has limitations as a stand‐alone treatment due to radiation resistance and safety as it affects even normal tissues. Although ferroptosis‐inducing drugs help alleviate radiation resistance, there are no safe ferroptosis‐inducing drugs that can be considered for clinical application and are still in the research stage. Here, the effectiveness of combined treatment with radiotherapy with Fe and hyaluronic acid‐based nanoparticles (FHA‐NPs) to directly induce ferroptosis, considering the clinical applications is reported. Through the induction of ferroptosis by FHA‐NPs and apoptosis by X‐ray irradiation, the therapeutic efficiency of cancer is greatly improved both in vitro and in vivo. In addition, Monte Carlo simulations are performed to assess the physical interactions of the X‐rays with the iron‐oxide nanoparticle. The study provides a deeper understanding of the synergistic effect of ferroptosis and X‐ray irradiation combination therapy. Furthermore, the study can serve as a valuable reference for elucidating the role and mechanisms of ferroptosis in radiation therapy.

Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation

“…The concentration of FHA NPs was chosen according to our earlier papers on FHA nanoparticles, while the concentration of GNPs was chosen from the literature regarding GNP uptake. 17,38–41 Thereafter, cells were kept in an incubator for 12 h for cellular uptake.…”

“…14 Reports indicate that a synergistic effect can be achieved by inducing ferroptosis, thereby diminishing radiation resistance. 15–17 Nevertheless, ferroptosis regulators, including SLCA7A11, GPX4, and GSH, play a major role in preventing ferroptosis subsequent to radiation exposure through the modulation of lipid peroxide levels induced by the heightened presence of reactive oxygen species (ROS). For this reason, ferroptosis-inducing nanoparticles have been proposed as a novel type of radiosensitizers.…”

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

“… 13 Also, ferroptosis induction therapy can be used in combination with conventional tumor treatments to enhance their therapeutic effects in certain malignancies. 14 …”

“…13 Also, ferroptosis induction therapy can be used in combination with conventional tumor treatments to enhance their therapeutic effects in certain malignancies. 14 Ferroptosis-inducing therapies have emerged as a crucial strategy in oncology, with ongoing advancements in the development and study of various small molecule drugs targeting ferroptosis-regulating pathways. 15 This review provides an overview of the regulatory mechanisms of ferroptosis and delves into the mechanisms of traditional small molecule ferroptosis inducers and their effects on various tumors.…”