研究动态
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NGR肽对阿霉素磷脂递送系统的疗效的影响。

Effect of an NGR Peptide on the Efficacy of the Doxorubicin Phospholipid Delivery System.

发表日期:2023 Aug 01
作者: Lyubov V Kostryukova, Yulia A Tereshkina, Elena G Tikhonova, Yulia Yu Khudoklinova, Daria V Bobrova, Alisa M Gisina, Galina E Morozevich, Veronica V Pronina, Tatiana V Bulko, Victoria V Shumyantseva
来源: Cell Death & Disease

摘要:

本研究是对以前开发的阿霉素磷脂递送系统的性质影响进行的一项调查的延续,该研究针对的是一种具有NGR的靶向组分,NGR肽具有与肿瘤细胞膜表面上的氨肽酶N(即CD13标记物)具有亲和性的特点,并已广泛应用于药物递送系统的靶向。本文展示了一项研究,该研究调查了带有或不带有肽链的磷脂组成的物理性质:颗粒大小、Zeta电位、在液体中的稳定性以及不同pH值(5.0、6.5、7.4)下纳米颗粒中阿霉素释放的依赖性。实验还显示出组成物的细胞毒性效应取决于孵化药物的剂量、组成中的靶向组分的存在以及物质的孵化时间。对于HT-1080(CD13阳性)和MCF-7(CD13阴性)细胞的细胞死亡途径分析表明,死亡主要是通过凋亡发生的。我们还提供了关于嵌入靶向肽的阿霉素磷脂纳米颗粒对DNA的影响的数据,该机制是通过静电相互作用实现的,通过差分脉冲伏安法进行了评估。通过差分脉冲伏安法对嵌入靶向肽的阿霉素磷脂纳米颗粒与天然dsDNA的相互作用进行了电化学研究。在这里,我们强调了阿霉素组成中的靶向肽使药物与dsDNA的特异相互作用从嵌合模式转变为静电相互作用。
This study is a continuation of an investigation into the effect of a targeted component, a peptide with an NGR, on the properties of the previously developed doxorubicin phospholipid delivery system. The NGR peptide has an affinity for aminopeptidase N (known as the CD13 marker on the membrane surface of tumor cells) and has been extensively used to target drug delivery systems. This article presents the results of a study investigating the physical properties of the phospholipid composition with and without the peptide chain: particle size, zeta potential, stability in fluids, and dependence of doxorubicin release from nanoparticles at different pH levels (5.0, 6.5, 7.4). The cytotoxic effect of the compositions has also been shown to depend on the dose of the drug used for incubation, the presence of the targeted component in the composition, and the time of incubation time of the substances. There was a significant difference in the cytotoxic effect on HT-1080 (CD13-positive) and MCF-7 (CD13-negative) cells. Cell death pathway analysis has shown that death occurred mainly by apoptosis. We also present data on the effect of doxorubicin embedded in phospholipid nanoparticles with the targeted peptide on DNA assessed by differential pulse voltammetry, the mechanism of action being electrostatic interactions. The interactions of native dsDNA with doxorubicin encapsulated in phospholipid nanoparticles with the targeted peptide were studied electrochemically by differential pulse voltammetry. Here, we have highlighted that the targeted peptide in the doxorubicin composition moved specific interaction of the drug with dsDNA from intercalative mode to electrostatic interactions.