Main Chain Polysulfoxides as Active 'Stealth' Polymers with Additional Antioxidant and Anti-Inflammatory Behaviour
Main Chain Polysulfoxides as Active 'Stealth' Polymers with Additional Antioxidant and Anti-Inflammatory Behaviour
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DOI：
10.3390/ijms20184583
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发表时间：
2019-09-02
影响因子：
5.6
通讯作者：
Tirelli, Nicola
中科院分区：
文献类型：
--
作者：
El Mohtadi, Farah;d'Arcy, Richard;Tirelli, Nicola
我们提出了一种基于亚硫醚的聚合物(聚丙二亚砜，PPSO)作为潜在的“隐形”大分子，同时作为一种具有药理活性(抗炎/抗氧化)的材料的评价。这两个概念的结合乍一看似乎很奇怪，因为生物材料和药物输送中的黄金标准聚合物--聚乙二醇(PEG)--由于其化学和生物惰性而是“隐形”的，这使得它几乎没有生物活性。相反，聚亚硫醚可能会在动态平衡条件下对生物分子产生相当大的惰性，并有可能清除与炎症相关的活性氧物种(ROS)。因此，聚亚硫醚是一种非常独特的“活性”“隐形”聚合物。在这里，我们描述了聚丙硫醚(PPS)的控制氧化合成PPSO，而PPS又是通过阴离子开环聚合得到的。在体外，PPSO的毒性较低(24 h对人皮肤成纤维细胞的IC50接近7 mg/mL)，补体活化水平(人血浆)和巨噬细胞摄取略低于同等大小的聚乙二醇。重要的是，与聚乙二醇不同的是，在内毒素激活的巨噬细胞上，PPSO显示出强烈的和剂量依赖的ROS(过氧化氢和次氯酸盐)清除活性，导致细胞因子的产生相应减少。
We present the evaluation of a sulfoxide-based polymer (poly(propylene sulfoxide), PPSO) as a potential 'stealth' macromolecule, and at the same time as a pharmacologically active (anti-inflammatory/anti-oxidant) material. The combination of these two concepts may at first seem peculiar since the gold standard polymer in biomaterials and drug delivery, poly(ethylene glycol) (PEG), is 'stealth' due to its chemical and biological inertness, which makes it hardly biologically active. Polysulfoxides, on the contrary, may couple a substantial inertness towards biomolecules under homeostatic conditions, with the possibility to scavenge reactive oxygen species (ROS) associated to inflammation. Polysulfoxides, therefore, are rather uniquely, 'active' 'stealth' polymers. Here, we describe the synthesis of PPSO through controlled oxidation of poly(propylene sulfide) (PPS), which on its turn was obtained via anionic ring-opening polymerization. In vitro, PPSO was characterized by a low toxicity (IC50 similar to 7 mg/mL at 24 h on human dermal fibroblasts) and a level of complement activation (in human plasma) and macrophage uptake slightly lower than PEG of a similar size. Importantly, and differently from PEG, on LPS-activated macrophages, PPSO showed a strong and dose-dependent ROS (hydrogen peroxide and hypochlorite)-scavenging activity, which resulted in a corresponding reduction of cytokine production.