Department of Mechanical & Aerospace Engineering, University of Texas, Arlington, Texas 76019, USA.
Mol Pharm. 2011 Apr 4;8(2):368-74. doi: 10.1021/mp1002398. Epub 2011 Jan 26.
In this work, we have combined constant-pH molecular dynamics simulations and experiments to provide a quantitative analysis of pH dependent interactions between doxorubicin hydrochloride (DOX) cancer therapeutic and faceted nanodiamond (ND) nanoparticle carriers. Our study suggests that when a mixture of faceted ND and DOX is dissolved in a solvent, the pH of this solvent plays a controlling role in the adsorption of DOX molecules on the ND. We find that the binding of DOX molecules on ND occurs only at high pH and requires at least ∼10% of ND surface area to be fully titrated for binding to occur. As such, this study reveals important mechanistic insight underlying an ND-based pH-controlled therapeutic platform.
在这项工作中，我们结合了恒 pH 分子动力学模拟和实验，对盐酸多柔比星 (DOX) 癌症治疗药物与多面纳米金刚石 (ND) 纳米颗粒载体之间 pH 依赖性相互作用进行了定量分析。我们的研究表明，当多面 ND 和 DOX 的混合物溶解在溶剂中时，溶剂的 pH 对 DOX 分子在 ND 上的吸附起着控制作用。我们发现，只有在高 pH 下，DOX 分子才会与 ND 结合，并且至少需要 ND 表面面积的约 10% 被完全滴定才能发生结合。因此，这项研究揭示了基于 ND 的 pH 控制治疗平台的重要机制见解。
