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基于硫酸软骨素的胶束纳米凝胶的自组装形成用于向乳腺癌细胞递送姜黄素。

Self-assembled formation of chondroitin sulfate-based micellar nanogel for curcumin delivery to breast cancer cells.

机构信息

Department of Biomedical Engineering, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.

Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.

出版信息

Int J Biol Macromol. 2020 Oct 15;161:771-778. doi: 10.1016/j.ijbiomac.2020.06.108. Epub 2020 Jun 13.

Abstract

Nanogel based drug delivery systems have been broadly used for cancer treatment. In this research, octadecylamine was grafted to chondroitin sulfate using three different mole ratios (10, 20, and 30) and named CS-ODA1, 2, and 3, respectively. The amide bond formation between chondroitin sulfate and octadecylamine was confirmed by 1H-nuclear magnetic resonance (HNMR) in the CS-ODA3 sample; therefore, further analysis was performed on this sample. Curcumin was loaded at defined Cur/CS-ODA ratios (5, 10 and 15%) and CS-ODA3 with 10% curcumin was selected for further experiments due to more entrapment efficiency (79.56% ± 5.56). In vitro release profile of the curcumin loaded nanogels showed >80% release after 70 h. In addition, the results of MTT analysis on the MCF-7 cell line showed almost no toxicity toward blank nanogels, while curcumin-loaded nanogels induced significant death after 24 h. In the end, analysis of the cell cycle using MCF-7 cells also confirmed the cytotoxicity of curcumin loaded nanogels. This study also showed that the presence of curcumin loaded chondroitin sulfate nanogels could successfully increase cellular uptake in comparison with free curcumin. The synthesized nanogels containing curcumin are expected to be effective for further studies in cancer treatment.

摘要

基于纳米凝胶的药物输送系统已广泛用于癌症治疗。在这项研究中,十八胺通过三种不同的摩尔比(10、20 和 30)接枝到硫酸软骨素上,并分别命名为 CS-ODA1、2 和 3。在 CS-ODA3 样品中通过 1H 核磁共振(HNMR)证实了硫酸软骨素和十八胺之间酰胺键的形成;因此,对该样品进行了进一步分析。姜黄素以确定的 Cur/CS-ODA 比(5、10 和 15%)加载到纳米凝胶中,由于包封效率更高(79.56%±5.56),因此选择载有 10%姜黄素的 CS-ODA3 进行进一步实验。载有姜黄素的纳米凝胶的体外释放曲线显示,70 小时后释放超过 80%。此外,MTT 分析 MCF-7 细胞系的结果表明,空白纳米凝胶几乎没有毒性,而载有姜黄素的纳米凝胶在 24 小时后诱导显著死亡。最后,使用 MCF-7 细胞对细胞周期的分析也证实了载有姜黄素的纳米凝胶的细胞毒性。这项研究还表明,与游离姜黄素相比,载有姜黄素的硫酸软骨素纳米凝胶的存在能够成功增加细胞摄取。含有姜黄素的合成纳米凝胶有望在癌症治疗的进一步研究中发挥作用。

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