Simultaneous Cross-Linking and Cross-Polymerization of Enzyme Responsive Polyethylene Glycol Nanogels in Confined Aqueous Droplets for Reduction of Low-Density Lipoprotein Oxidation,Biomacromolecules

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Simultaneous Cross-Linking and Cross-Polymerization of Enzyme Responsive Polyethylene Glycol Nanogels in Confined Aqueous Droplets for Reduction of Low-Density Lipoprotein Oxidation
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-10-30 , DOI: 10.1021/acs.biomac.0c01238
Suman Basak ₁ , Harshvardhan Ajay Khare _{1,

2} , Martin Roursgaard ₃ , Paul J Kempen ₁ , Jong Hyun Lee ₁ , Salime Bazban-Shotorbani ₁ , Martin Kræmer ₁ , Sergey Chernyy ₁ , Thomas L Andresen ₁ , Kristoffer Almdal ₄ , Nazila Kamaly _{1,

5}

Affiliation

A key initiating step in atherosclerosis is the accumulation and retention of apolipoprotein B complexing lipoproteins within the artery walls. In this work, we address this exact initiating mechanism of atherosclerosis, which results from the oxidation of low-density lipoproteins (oxLDL) using therapeutic nanogels. We present the development of biocompatible polyethylene glycol (PEG) cross-linked nanogels formed from a single simultaneous cross-linking and co-polymerization step in water without the requirement for an organic solvent, high temperature, or shear stress. The nanogel synthesis also incorporates in situ noncovalent electrostatically driven template polymerization around an innate anti-inflammatory and anti-oxidizing paraoxonase-1 (PON-1) enzyme payload—the release of which is triggered because of matrix metalloproteinase responsive elements instilled in the PEG cross-linker monomer. The results obtained demonstrate the potential of triggered release of the PON-1 enzyme and its efficacy against the production of ox-LDL, and therefore a reduction in macrophage foam cell and reactive oxygen species formation.

中文翻译：

同时交联和交叉聚合反应的聚乙二醇纳米凝胶在封闭的水滴中，以减少低密度脂蛋白的氧化

动脉粥样硬化的关键启动步骤是载脂蛋白B复合脂蛋白在动脉壁内的积聚和保留。在这项工作中，我们解决了动脉粥样硬化的这种确切的引发机制，这是由使用治疗性纳米凝胶的低密度脂蛋白（oxLDL）的氧化引起的。我们目前正在开发生物相容性聚乙二醇（PEG）交联纳米凝胶，该纳米凝胶由水中的单个同时交联和共聚步骤形成，而不需要有机溶剂，高温或剪切应力。纳米凝胶合成也可以原位结合非共价静电驱动模板聚合反应围绕先天性抗炎和抗氧化对氧磷酶-1（PON-1）酶有效负载—释放该释放是由于滴入PEG交联剂单体中的基质金属蛋白酶响应元素所致。获得的结果证明了PON-1酶触发释放的潜力及其对ox-LDL产生的功效，因此减少了巨噬细胞泡沫细胞和活性氧的形成。

更新日期：2020-10-30

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