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工程化动态硼酸酯介导的可自愈合生物相容性G-四链体水凝胶用于维生素的持续释放

Engineered Dynamic Boronate Ester-Mediated Self-Healable Biocompatible G-Quadruplex Hydrogels for Sustained Release of Vitamins.

作者信息

Ghosh Tapas, Biswas Ankan, Gavel Pramod K, Das Apurba K

机构信息

Department of Chemistry , Indian Institute of Technology Indore , Indore 453552 , India.

出版信息

Langmuir. 2020 Feb 18;36(6):1574-1584. doi: 10.1021/acs.langmuir.9b03837. Epub 2020 Feb 6.

Abstract

Injectable, self-healable, and biocompatible dynamic hydrogels prepared from the molecular self-assembly and reversible covalent bond formation of low-molecular-weight hydrogelators are increasing in the field of drug delivery. Herein, we report the formation of G-quadruplex hydrogels via the multicomponent self-assembly and reversible bond formation between guanosine (G) and 1-naphthaleneboronic acid in the presence of the monovalent cation K. The cation-templated stacking interaction of G4 quartets and the formation of dynamic cyclic boronate esters are responsible for the construction of dynamic G-quadruplex assembly. The in situ-synthesized dynamic cyclic boronate esters are well characterized by B nuclear magnetic resonance and Fourier transform infrared spectroscopy methods. The formation and morphology of the G-quadruplex hydrogel are well supported by several spectroscopic and microscopic techniques. The injectability and self-healing ability of the G-quadruplex hydrogel are also investigated. The in vivo cytotoxicity of the G-quadruplex hydrogel is extensively evaluated over different cell lines (HeLa, MCF-7, and HEK293) to observe the biostability and broad-spectrum biocompatibility of the hydrogel. Further, this injectable, biocompatible G-quadruplex hydrogel has been used for encapsulation and sustained release of two important vitamins (B and B) over 40 h at physiological pH (7.46) and temperature (37 °C) without the influence of any external stimuli.

摘要

由低分子量水凝胶剂的分子自组装和可逆共价键形成制备的可注射、自愈合且生物相容的动态水凝胶在药物递送领域中日益受到关注。在此,我们报道了在单价阳离子K存在下,通过鸟苷(G)与1-萘硼酸之间的多组分自组装和可逆键形成形成G-四链体水凝胶。G4四重体的阳离子模板堆积相互作用和动态环状硼酸酯的形成负责动态G-四链体组装的构建。原位合成的动态环状硼酸酯通过硼核磁共振和傅里叶变换红外光谱方法得到了很好的表征。G-四链体水凝胶的形成和形态得到了多种光谱和显微镜技术的有力支持。还研究了G-四链体水凝胶的可注射性和自愈合能力。在不同细胞系(HeLa、MCF-7和HEK293)上广泛评估了G-四链体水凝胶的体内细胞毒性,以观察水凝胶的生物稳定性和广谱生物相容性。此外,这种可注射、生物相容的G-四链体水凝胶已用于在生理pH(7.46)和温度(37°C)下40小时内封装和持续释放两种重要维生素(B和B),而不受任何外部刺激的影响。

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