Acridine Orange Encapsulated Mesoporous Manganese Dioxide Nanoparticles to Enhance Radiotherapy

Manganese dioxide (MnO₂) nanoparticles are a promising type of radiosensitizer for they can catalyze H₂O₂ decomposition to produce O₂. Combining MnO₂ nanoparticles with conventional, small molecule radiosensitizers would further enhance radiotherapy (RT) efficacy due to complementary mechanisms of action. However, solid MnO₂ nanoparticles are suboptimal at drug loading, limiting the related progress. Herein we report a facile method to synthesize mesoporous MnO₂ (mMnO₂) nanoparticles, which can efficiently encapsulate small molecule therapeutics. In particular, we found that acridine orange (AO), a small molecule radiosensitizer, can be loaded onto mMnO₂ nanoparticles at very high efficiency and released to the surroundings in a controlled fashion. We show that mMnO₂ nanoparticles can efficiently produce O₂ inside cells. This, together with AO-induced DNA damage, significantly enhances RT outcomes, which was validated both in vitro and in vivo. Meanwhile, mMnO₂ nanoparticles slowly degrade in acidic environments to release Mn²⁺, providing a facile way to keep track of the nanoparticles through magnetic resonance imaging (MRI). Overall, our studies suggest mMnO₂ as a promising nanoplatform that can be exploited to produce composite radiosensitizers for RT.