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沸石负载的吖啶类化合物能否提高其抗癌性能?

Can Zeolite-Supporting Acridines Boost Their Anticancer Performance?

作者信息

Ranković Maja, Jevremović Anka, Janošević Ležaić Aleksandra, Arsenijević Aleksandar, Rupar Jelena, Dobričić Vladimir, Nedić Vasiljević Bojana, Gavrilov Nemanja, Bajuk-Bogdanović Danica, Milojević-Rakić Maja

机构信息

University of Belgrade-Faculty of Physical Chemistry, 11000 Belgrade, Serbia.

Department of Physical Chemistry and Instrumental Methods, University of Belgrade-Faculty of Pharmacy, 11221 Belgrade, Serbia.

出版信息

J Funct Biomater. 2023 Mar 22;14(3):173. doi: 10.3390/jfb14030173.

Abstract

Acridine and its derivatives (9-chloroacridine and 9-aminoacridine) are investigated here, supported on FAU type zeolite Y, as a delivery system of anticancer agents. FTIR/Raman spectroscopy and electron microscopy revealed successful drug loading on the zeolite surface, while spectrofluorimetry was employed for drug quantification. The effects of the tested compounds on cell viability were evaluated using in vitro methylthiazol-tetrazolium (MTT) colorimetric technique against human colorectal carcinoma (cell line HCT-116) and MRC-5 fibroblasts. Zeolite structure remained unchanged during homogeneous drug impregnation with achieved drug loadings in the 18-21 mg/g range. The highest drug release, in the µM concentration range, with favourable kinetics was established for zeolite-supported 9-aminoacridine. The acridine delivery via zeolite carrier is viewed in terms of solvation energy and zeolite adsorption sites. The cytotoxic effect of supported acridines on HCT-116 cells reveals that the zeolite carrier improves toxicity, while the highest efficiency is displayed by zeolite-impregnated 9-aminoacridine. The 9-aminoacridine delivery via zeolite carrier favours healthy tissue preservation while accompanying increased toxicity toward cancer cells. Cytotoxicity results are well correlated with theoretical modelling and release study, providing promising results for applicative purposes.

摘要

本文研究了负载于FAU型Y沸石上的吖啶及其衍生物(9-氯吖啶和9-氨基吖啶)作为抗癌药物递送系统的情况。傅里叶变换红外光谱/拉曼光谱和电子显微镜显示药物成功负载在沸石表面,同时采用荧光分光光度法进行药物定量。使用体外甲基噻唑四氮唑(MTT)比色技术评估了受试化合物对人结肠癌细胞系HCT-116和MRC-5成纤维细胞活力的影响。在均相药物浸渍过程中,沸石结构保持不变,药物负载量达到18-21 mg/g范围。对于负载在沸石上的9-氨基吖啶,在µM浓度范围内实现了最高的药物释放,且释放动力学良好。通过溶剂化能和沸石吸附位点来考察通过沸石载体递送吖啶的情况。负载的吖啶对HCT-116细胞的细胞毒性作用表明,沸石载体提高了毒性,而负载9-氨基吖啶的沸石显示出最高的效率。通过沸石载体递送9-氨基吖啶有利于保护健康组织,同时对癌细胞的毒性增加。细胞毒性结果与理论建模和释放研究密切相关,为应用目的提供了有前景的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f783/10056282/bf6848bf301b/jfb-14-00173-g001.jpg

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