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.

中文翻译：

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cr啶橙包裹的中孔二氧化锰纳米颗粒可增强放射治疗效果。

二氧化锰（MnO2）纳米粒子是一种有前途的放射增敏剂，因为它们可以催化H2O2分解生成O2。由于互补的作用机制，将MnO2纳米粒子与常规的小分子放射增敏剂结合使用将进一步增强放射疗法（RT）的功效。但是，固体MnO2纳米颗粒在药物加载时次优，从而限制了相关进展。在这里，我们报告了一种简便的方法来合成介孔MnO2（mMnO2）纳米粒子，它可以有效地封装小分子治疗剂。尤其是，我们发现cr啶橙（AO）是一种小分子放射增敏剂，可以非常高效地加载到mMnO2纳米颗粒上，并以可控的方式释放到周围环境中。我们表明，mMnO2纳米粒子可以有效地在细胞内产生O2。这，与AO诱导的DNA损伤一起，可显着增强RT效果，这在体外和体内均得到了验证。同时，mMnO2纳米颗粒在酸性环境中缓慢降解以释放Mn2 +，从而提供了一种通过磁共振成像（MRI）跟踪纳米颗粒的简便方法。总体而言，我们的研究表明mMnO2是一种很有前途的纳米平台，可用于生产RT复合放射增敏剂。