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紫杉醇与金刚石纳米颗粒联合作用对人血清白蛋白(HSA)结构的影响及其对 MDA-MB-231 细胞的抗增殖作用。

The Effects of Paclitaxel in the Combination of Diamond Nanoparticles on the Structure of Human Serum Albumin (HSA) and Their Antiproliferative Role on MDA-MB-231cells.

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

出版信息

Protein J. 2020 Jun;39(3):268-283. doi: 10.1007/s10930-020-09882-4.

Abstract

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.

摘要

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。

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