Ferroptosis driven by nanoparticles for tackling glioblastoma
Ana Carlos, Maria Mendes, Maria Teresa Cruz, Alberto A. C. C. Pais, Carla Vitorino
Abstract
Glioblastoma (GBM) is the most aggressive, malignant, and drug-resistant brain tumor. There are no effective treatment options for GBM, which usually leads to relapses that cause patients to die a few months later. Ferroptosis, a newly discovered mechanism of regulated cell death, has been identified as a tumor suppressor in solid tumors and represents an alternative to apoptosis resistance. This mechanism of cell death is characterized by iron overload, which is responsible for generating reactive oxygen species (ROS) in the cell. Understanding the ferroptosis pathway and its key regulators can be used to develop rational delivery systems that specifically target these regulators in GBM cells and promote cell death. This review conducted a systematic literature search to better understand the potential of ferroptosis as a target for developing nanoparticles to tackle GBM. The mechanisms of action, design parameters, efficacy, and safety concerns of 16 nanoparticles were evaluated, demonstrating the potential of combining ferroptosis inducers with nanocarriers to promote a selective delivery to the tumor microenvironment. Harnessing Ferroptosis: A Novel Approach to Target Glioblastoma. • Nanoparticles may effectively induce ferroptosis in drug-resistant glioblastoma. • Ferroptosis regulators targeted by nanoparticles offer new GBM treatment avenues. • Rational design of nanocarriers enhances selectivity and efficacy in GBM therapy. • In vivo studies show nanoparticle-induced ferroptosis may reduce GBM tumor size. • Nanoparticle strategies for GBM demonstrate potential for clinical development.