Multifunctional MnO₂-based nanoplatform-induced ferroptosis and apoptosis for synergetic chemoradiotherapy

Background: Radiosensitizers that can effectively consume glutathione provide broad prospects for enhancing the efficacy and reducing the side effects of radiotherapy. Aim: To explore the potential role of CuS@mSiO₂@MnO₂ nanocomposites in synergetic chemoradiotherapy. Methods: Nanocomposites were characterized by transmission electron microscopy, UV-Vis spectrometry and dynamic light scattering and were loaded with doxorubicin (DOX). The uptake and biodistribution of nanocomposites were observed by CCK8 assay, MRI and confocal laser scanning microscopy. The radiosensitization effect of nanocomposites and nanocomposites/DOX was assessed both in vitro and in vivo. Results:In vitro application of nanocomposites, with an average diameter of 30 nm and ζ-potential of 13.2 ± 0.4 mV, in combination with radiotherapy, depleted glutathione and induced ferroptosis and apoptosis. Nanocomposites/DOX exhibited tumor cell damage in vivo. Conclusion: We propose that this glutathione-depleting nanosystem could be a radiosensitizer as well as a drug transporter.