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负载 Ru(II)(--柠烯)配合物的氧化石墨烯:一种有效的 pH 响应性抗癌药物传递系统。

Ru(II)(--cymene) Conjugates Loaded onto Graphene Oxide: An Effective pH-Responsive Anticancer Drug Delivery System.

机构信息

Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.

School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, MC, Italy.

出版信息

Molecules. 2022 Nov 5;27(21):7592. doi: 10.3390/molecules27217592.

Abstract

Graphene oxide-based nanodrug delivery systems are considered one of the most promising platforms to deliver therapeutic drugs at the target site. In this study, Ru(II)(6--cymene) complexes containing the benzothiazole ligand were covalently anchored on graphene oxide using the ultrasonication method. The nanoconjugates GO-NCD- and GO-NCD- were characterized by FT-IR, UV-visible, NMR, TGA, SEM, and TEM techniques, which confirmed the successful loading of both the complexes (NCD and NCD ) on the carrier with average particle diameter sizes of 17 ± 6.9 nm and 25 ± 6.5 nm. In vitro DNA binding studies of the nanoconjugates were carried out by employing various biophysical methods to investigate the binding interaction with the therapeutic target biomolecule and to quantify the intrinsic binding constant values useful to understand their binding affinity. Our results suggest (i) high and values of the graphene-loaded conjugates (ii) effective cleavage of plasmid DNA at a lower concentration of 7.5 µM and 10 µM via an oxidative pathway, and (iii) fast release of NCD at an acidic pH that could have a good impact on the controlled delivery of drug. It was found that 90% of the drug was released in an acidic pH (5.8 pH) environment in 48 h, therefore suggesting pH-responsive behavior of the drug delivery system. Molecular docking, DFT studies, and cytotoxicity activity against three cancer cell lines by SRB assay were also performed.

摘要

基于氧化石墨烯的纳米药物递送系统被认为是将治疗药物递送到靶位的最有前途的平台之一。在这项研究中,采用超声法将含有苯并噻唑配体的钌(II)(6- 枯烯)配合物共价锚定在氧化石墨烯上。通过 FT-IR、UV-可见、NMR、TGA、SEM 和 TEM 技术对纳米复合物 GO-NCD- 和 GO-NCD-进行了表征,证实了两种配合物(NCD 和 NCD )成功地负载在载体上,平均粒径分别为 17±6.9nm 和 25±6.5nm。通过采用各种生物物理方法进行纳米复合物的体外 DNA 结合研究,研究了与治疗靶标生物分子的结合相互作用,并定量了固有结合常数值,有助于理解它们的结合亲和力。我们的结果表明:(i)负载氧化石墨烯的缀合物具有高 和 值;(ii)在较低浓度(7.5µM 和 10µM)下通过氧化途径有效切割质粒 DNA;(iii)在酸性 pH 下快速释放 NCD ,这可能对药物的控制释放有很好的影响。研究发现,在 48 小时内,90%的药物在酸性 pH(5.8 pH)环境中释放,因此表明药物递送系统具有 pH 响应行为。还进行了分子对接、DFT 研究以及 SRB 测定法对三种癌细胞系的细胞毒性活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41e/9655566/c454e4b18ea8/molecules-27-07592-sch001.jpg

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