文章：

双羟基盐作为6-巯基嘌呤的智能生物相容性pH响应载体

Double Hydroxyl Salt as Smart Biocompatible pH-Responsive Carrier for 6-Mercaptopurine

原文发布日期：30 November 2023

DOI: 10.3390/cancers15235670

类型: Article

开放获取: 是

英文摘要：

Hydroxy double salts are layered materials that are considered to be biocompatible. For this reason, research has been initiated on the possibility of their use in drug delivery. Despite their use for several types of drugs, their potential for controlled release of mercaptopurine (MERC) has not been studied. In this work, the synthesized hydroxy double salt (HDS) material was used as a carrier for this drug for the first time. The effectiveness of HDS synthesis has been proven by such techniques as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Based on the FT-IR and energy-dispersive X-ray spectroscopy (EDS) results, the effectiveness of drug sorption was proven. The exact amount of drug retained was determined by the UV-Vis technique. The obtained results indicate that the drug is evenly distributed on the surface of the carrier, which is important during the controlled delivery of drugs. In the most important stage of the research, the effectiveness of drug release in response to changes in the pH of the environment was proven. The drug is not released into an environment that mimics healthy human tissues. It is released only after contact with the acidic environment that usually surrounds cancer cells. The low cellular toxicity of HDS and significant cytotoxic effect of HDS-MERC were confirmed by in vitro studies on MCF-7 human breast and DU145 prostate cancer cell lines and non-cancerous keratinocytes HaCaT. Interestingly, coupling with the HDS carrier increased the cytotoxic effect of MERC towards DU145 cells. Such an “intelligent” drug carrier for mercaptopurine has not been previously described in the literature. The obtained results indicate its great potential.

摘要翻译： 

羟基双层盐是一种层状材料，被认为具有生物相容性。因此，人们已开始研究其作为药物载体的可能性。尽管该材料已用于多种药物递送，但其对巯基嘌呤的控释潜力尚未得到研究。本研究首次采用合成的羟基双层盐材料作为该药物的载体。通过X射线衍射、傅里叶变换红外光谱和扫描电子显微镜等技术验证了羟基双层盐合成的有效性。基于傅里叶变换红外光谱和能量色散X射线光谱结果，证实了药物吸附的有效性。药物保留的具体含量通过紫外-可见光谱技术测定。研究结果表明药物均匀分布在载体表面，这对药物控释过程具有重要意义。在研究最关键阶段，证实了药物释放效率会响应环境pH值变化。在模拟健康人体组织的环境中药物不会释放，仅在与癌细胞周围常见的酸性环境接触后才开始释放。通过对MCF-7人乳腺癌细胞、DU145前列腺癌细胞系及非癌性角质形成细胞HaCaT的体外研究，证实了羟基双层盐的低细胞毒性及羟基双层盐-巯基嘌呤复合物的显著细胞毒效应。值得注意的是，与羟基双层盐载体结合增强了巯基嘌呤对DU145细胞的细胞毒作用。这种针对巯基嘌呤的"智能"药物载体在既往文献中尚未见报道，所得结果表明其具有巨大应用潜力。

原文链接：

Double Hydroxyl Salt as Smart Biocompatible pH-Responsive Carrier for 6-Mercaptopurine