Antitumor effects of magnesium-based materials through the ferroptosis pathway

Magnesium-based materials offer unique advantages in clinical applications owing to their biodegradability and osteogenic activity; however, the excessively rapid degradation of pure magnesium limits its clinical translation. This review systematically integrates the latest advances in magnesium-based materials from both materials engineering and tumor biology perspectives. At the materials engineering level, it focuses on the roles of alloying and surface coating technologies in controlling degradation kinetics and optimizing functionality, and summarizes preclinical and clinical evidence for various magnesium-based material systems. At the tumor biology level, this review first discusses the physiological, therapeutic, and toxic concentration ranges of Mg 2+ . Subsequently, it proposes an integrated perspective that Mg 2+ , OH⁻, and H 2 may act across three functional dimensions—immune effector enhancement, neutralization of the acidic tumor microenvironment (TME), and redox protection—to form a cooperative network. In addition, this review highlights inconsistent findings in the existing literature. Finally, it further integrates immune–ferroptosis crosstalk and discusses the potential role of ferroptosis as a "signal amplifier" within this network, while systematically identifying key evidence gaps. Importantly, because of the precipitation equilibrium between Mg 2+ and OH⁻and the physical barrier effect of H₂ bubbles, the spatial distributions of these three degradation products are not independent; instead, they exhibit a compartmentalized pattern governed by thermodynamic and kinetic coupling, which constitutes a fundamental constraint that must be considered when investigating their synergistic effects. Nevertheless, current research still has several deficiencies: the effects of the three degradation products when they coexist have not been systematically evaluated; clinical translation remains insufficient; and the ferroptosis-inducing capacity has not been adequately validated. Looking ahead, a pragmatic positioning of magnesium-based materials is as a multifunctional synergistic platform that can be sequentially combined with ferroptosis inducers (FINs), immune checkpoint inhibitors, or standard chemotherapeutic regimens, ultimately advancing an integrated therapeutic strategy that unites mechanical support, tissue repair, and TME modulation.