Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Protein J. 2020 Jun;39(3):268-283. doi: 10.1007/s10930-020-09882-4.
Since the interactions of anti-cancer agents with blood constituents, in particular with human serum albumin (HSA) may have a major impact on drug pharmacology, the present study designed to provide a fundamental understanding of the interaction of nanodiamonds (NDs) together with paclitaxel (PTX) with HSA in detail for the first time. The UV-Vis, steady-state fluorescence, far-UV CD and zeta potential results displayed that PTX + NDs could form a complex with HSA. Additionally, the values of binding constants and ΔG showed that PTX + NDs interact strongly with HSA compared to PTX or NDs alone and the hydrophobic force plays a major role in this interaction. Moreover, the in vitro release behavior of PTX + NDs form HSA can be regulated at dissimilar pH levels. The anticancer property of 0.5 µM PTX + 20 µM NDs by MTT assay demonstrates that this combination can tremendously diminish the proliferation of MDA-MB-231cells compared to PTX or NDs alone. Altogether, the structure of HSA changed moderately in the presence of PTX + NDs and PTX + NDs can promote mortality of MDA-MB-231 cells besides those mortality effects induced via PTX or NDs alone. The results obtained from this study can help in understanding the pharmacokinetic properties of PTX + NDs.
由于抗癌药物与血液成分（尤其是人血清白蛋白（HSA））的相互作用可能对药物的药理学有重大影响，因此本研究旨在首次详细了解纳米金刚石（NDs）与紫杉醇（PTX）与 HSA 的相互作用。紫外可见分光光度法、稳态荧光、远紫外 CD 和 zeta 电位结果表明，PTX+NDs 可以与 HSA 形成复合物。此外，结合常数和ΔG 的值表明，与单独的 PTX 或 NDs 相比，PTX+NDs 与 HSA 强烈相互作用，疏水作用力在这种相互作用中起主要作用。此外，PTX+NDs 从 HSA 中的体外释放行为可以在不同的 pH 值水平下进行调节。MTT 法测定的 0.5µM PTX+20µM NDs 的抗癌性能表明，与单独的 PTX 或 NDs 相比，该组合可以极大地减少 MDA-MB-231 细胞的增殖。总的来说，在存在 PTX+NDs 的情况下，HSA 的结构发生了适度的变化，并且除了单独的 PTX 或 NDs 诱导的致死作用之外，PTX+NDs 还可以促进 MDA-MB-231 细胞的死亡。本研究的结果可以帮助理解 PTX+NDs 的药代动力学特性。
