Inducible Nitric Oxide Synthase Embedded in Alginate/Polyethyleneimine Hydrogel as a New Platform to Explore NO-Driven Modulation of Biological Function.

Inducible Nitric Oxide Synthase Embedded in Alginate/Polyethyleneimine Hydrogel as a New Platform to Explore NO-Driven Modulation of Biological Function.
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DOI:
10.3390/molecules28041612
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发表时间:
2023-02-07
期刊:
影响因子:
4.6
通讯作者:
Bayachou, Mekki
Bayachou, Mekki
中科院分区:
化学2区
文献类型:
--
作者:
Maher, Shaimaa;Smith, Lauren A.;El-Khoury, Celine A.;Kalil, Haitham;Sossey-Alaoui, Khalid;Bayachou, Mekki

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一氧化氮 (NO) 是一种小自由基分子,在生物学中普遍存在,并且对一系列生物活动(包括细胞生长和细胞凋亡)具有重大影响。该分子参与信号传导并影响许多生理功能。近几十年来,一些与癌症相关的过程,如血管生成、程序性细胞死亡、浸润、细胞周期进展和转移,都与一氧化氮有关。此外,其他并行工作表明 NO 也具有作为抗癌剂的潜力。因此,它在癌症相关治疗中引起了关注。一氧化氮合酶家族(NOS)是一氧化氮生物合成所必需的。开发一氧化氮释放材料作为强效杀肿瘤疗法变得越来越流行,这种材料可以向肿瘤部位持续输送高浓度的一氧化氮。在本文中,我们开发了基于海藻酸钠水凝胶的NO释放材料。在这方面,通过聚乙烯亚胺和 iNOS 加氧酶的吸附层对藻酸盐水凝胶盘进行了修饰。这些释放 NO 的水凝胶盘是使用逐层薄膜构建技术制备的。 iNOS 加氧酶吸附在带正电荷的聚乙烯亚胺 (PEI) 基质层上,该基质层形成于带负电荷的海藻酸钠水凝胶上。我们发现,当水凝胶材料暴露于含有 NOS 反应所需所有成分的溶液时,一氧化氮是由水凝胶材料中所含的酶产生的。通过 FTIR 测量和扫描电子显微镜证实了逐层过程的静电化学吸附。然后我们测试了所得改性海藻酸钠水凝胶盘的生物相容性。我们证明这种 NOS-PEI 修饰的水凝胶总体上与细胞生长相容。我们对 NOS/水凝胶薄膜进行了表征,并检查了它们在 NO 释放曲线方面的功能特征。然而,在活动的前 24 小时内,这些薄膜显示 NO 释放通量增加,随后逐渐下降,然后是稳定的 NO 释放期。这些发现显示了使用该系统作为 NO 驱动的生物功能(包括致癌作用)调节平台的内在潜力。
Nitric oxide (NO), a small free radical molecule, turned out to be pervasive in biology and was shown to have a substantial influence on a range of biological activities, including cell growth and apoptosis. This molecule is involved in signaling and affects a number of physiologic functions. In recent decades, several processes related to cancer, such as angiogenesis, programmed cell death, infiltration, cell cycle progression, and metastasis, have been linked with nitric oxide. In addition, other parallel work showed that NO also has the potential to operate as an anti-cancer agent. As a result, it has gained attention in cancer-related therapeutics. The nitric oxide synthase enzyme family (NOS) is required for the biosynthesis of nitric oxide. It is becoming increasingly popular to develop NO-releasing materials as strong tumoricidal therapies that can deliver sustained high concentrations of nitric oxide to tumor sites. In this paper, we developed NO-releasing materials based on sodium alginate hydrogel. In this regard, alginate hydrogel discs were modified by adsorbing layers of polyethyleneimine and iNOS-oxygenase. These NO-releasing hydrogel discs were prepared using the layer-by-layer film building technique. The iNOS-oxygenase is adsorbed on the positively charged polyethyleneimine (PEI) matrix layer, which was formed on a negatively charged sodium alginate hydrogel. We show that nitric oxide is produced by enzymes contained within the hydrogel material when it is exposed to a solution containing all the components necessary for the NOS reaction. The electrostatic chemical adsorption of the layer-by-layer process was confirmed by FTIR measurements as well as scanning electron microscopy. We then tested the biocompatibility of the resulting modified sodium alginate hydrogel discs. We showed that this NOS-PEI-modified hydrogel is overall compatible with cell growth. We characterized the NOS/hydrogel films and examined their functional features in terms of NO release profiles. However, during the first 24 h of activity, these films show an increase in NO release flux, followed by a gradual drop and then a period of stable NO release. These findings show the inherent potential of using this system as a platform for NO-driven modulation of biological functions, including carcinogenesis.
DOI: 10.1016/j.jddst.2019.101154
发表时间: 2019-10-01
影响因子: 5
作者:
Akbarzadeh, Mahdi;Oskuee, Reza Kazemi;Malaekeh-Nikouei, Bizhan
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影响因子: 2.2
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发表时间: 2015-05-03
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