Department of Chemistry , University of Georgia , Athens , Georgia 30602 , United States.
State Key Laboratory of Molecular Vaccinology and Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Fujian 361102 , China.
Bioconjug Chem. 2020 Jan 15;31(1):82-92. doi: 10.1021/acs.bioconjchem.9b00751. Epub 2019 Dec 19.
Manganese dioxide (MnO) nanoparticles are a promising type of radiosensitizer for they can catalyze HO decomposition to produce O. Combining MnO nanoparticles with conventional, small molecule radiosensitizers would further enhance radiotherapy (RT) efficacy due to complementary mechanisms of action. However, solid MnO nanoparticles are suboptimal at drug loading, limiting the related progress. Herein we report a facile method to synthesize mesoporous MnO (mMnO) nanoparticles, which can efficiently encapsulate small molecule therapeutics. In particular, we found that acridine orange (AO), a small molecule radiosensitizer, can be loaded onto mMnO nanoparticles at very high efficiency and released to the surroundings in a controlled fashion. We show that mMnO nanoparticles can efficiently produce O inside cells. This, together with AO-induced DNA damage, significantly enhances RT outcomes, which was validated both and . Meanwhile, mMnO nanoparticles slowly degrade in acidic environments to release Mn, providing a facile way to keep track of the nanoparticles through magnetic resonance imaging (MRI). Overall, our studies suggest mMnO as a promising nanoplatform that can be exploited to produce composite radiosensitizers for RT.
二氧化锰(MnO)纳米颗粒是一种很有前途的放射增敏剂,因为它们可以催化 HO 的分解产生 O。将 MnO 纳米颗粒与传统的小分子放射增敏剂结合使用,由于其作用机制互补,将进一步提高放射治疗(RT)的疗效。然而,固态 MnO 纳米颗粒的药物负载能力较差,限制了相关进展。在此,我们报告了一种简便的方法来合成介孔 MnO(mMnO)纳米颗粒,它可以有效地包裹小分子治疗药物。特别地,我们发现吖啶橙(AO),一种小分子放射增敏剂,可以非常高效地负载到 mMnO 纳米颗粒上,并以可控的方式释放到周围环境中。我们证明 mMnO 纳米颗粒可以在细胞内有效地产生 O。这与 AO 诱导的 DNA 损伤一起,显著增强了 RT 的效果,这在 和 中都得到了验证。同时,mMnO 纳米颗粒在酸性环境中缓慢降解以释放 Mn,通过磁共振成像(MRI)提供了一种简便的方法来跟踪纳米颗粒。总的来说,我们的研究表明 mMnO 是一种很有前途的纳米平台,可以用来制备用于 RT 的复合放射增敏剂。