Theranostic potential of manganese dioxide nanoparticles for targeting tumor hypoxia during MR-guided radiotherapy

Magnetic resonance (MR)-guided radiotherapy (MRgRT) is an attractive treatment option for many patients with cancer, allowing higher radiation doses to be safely delivered. However, even with more precise tumor targeting and higher doses, hypoxia remains an important clinical challenge, making tumors more radioresistant and detracting from the benefits of dose escalation. Nanoparticles loaded with manganese dioxide (MnO₂) have been developed as theranostic agents to improve MRgRT. We review the MR-enhancing and oxygen-generating properties of MnO₂ nanoparticles, the evidence that MnO₂ nanoparticles can improve tumor response to RT, and the opportunities for further research to support translation into the clinic.

The theranostic potential of MnO₂ nanoparticles lies in the dual functionality of providing tumor-specific MR enhancement for RT planning and image guidance, while also generating oxygen in the tumor microenvironment (TME) to overcome hypoxia-induced radioresistance. Several preclinical studies have demonstrated lower levels of hypoxia and improved tumor response when RT is combined with MnO₂ nanoparticles. In addition, MnO₂ nanoparticles have been reported to deplete intracellular antioxidants and create an immunogenic, less immunosuppressive TME, which may also enhance radiotherapy efficacy. These encouraging findings support further clinical evaluation in patients receiving MRgRT.