Abstract：
In this study, an efficient synthetic strategy and potential route to obtain a photo-reactive silver-containing cytosine-functionalized polypropylene glycol polymer (Ag-Cy-PPG) was developed by combining a hydrophilic oligomeric polypropylene glycol (PPG) backbone with dual pH-sensitive/photo-reactive cytosine-silver-cytosine (Cy-Ag-Cy) linkages. The resulting photo-responsive Ag-Cy-PPG holds great promise as a multifunctional biomedical material that generates spherical-like nanogels in water; the nanogels exhibit high antibacterial activity and thus may significantly enhance the efficacy of antibacterial treatment. Due to the formation of photo-dimerized Cy-Ag-Cy cross-linkages after UV irradiation, Ag-Cy-PPG converts into water-soluble cross-linked nanogels that possess a series of interesting chemical and physical properties, such as intense and stable fluorescence behavior, highly sensitive pH-responsive characteristics, on/off switchable phase transition behavior, and well-controlled release of silver ions (Ag+) in mildly acidic aqueous solution. Importantly, antibacterial tests clearly demonstrated that irradiated Ag-Cy-PPG nanogels exhibited strong antibacterial activity at low doses (MIC values of < 50 μg/mL) against gram-positive and gram-negative bacterial pathogens, whereas non-irradiated Ag-Cy-PPG nanogels did not inhibit the viability of bacterial pathogens. These results indicate that irradiated Ag-Cy-PPG nanogels undergo a highly sensitive structural change in the bacterial microenvironment due to their relatively unstable π-conjugated structures (compared to non-irradiated nanogels); this change results in a rapid structural response that promotes intracellular release of Ag+ and induces potent antibacterial ability. Overall, this newly created metallo-supramolecular system may potentially provide an efficient route to dramatically enhance the therapeutic effectiveness of antibacterial treatments.
摘要：
在这项研究中,通过将亲水性低聚聚丙二醇（PPG）主链与双重pH敏感/光反应性胞嘧啶-银-胞嘧啶（Cy-Ag-Cy）键结合，开发了一种有效的合成策略和潜在的途径来获得光反应性含银的胞嘧啶官能化聚丙二醇聚合物（Ag-Cy-PPG）。所得的光响应性Ag-Cy-PPG作为在水中产生球形纳米凝胶的多功能生物医学材料具有巨大的前景;纳米凝胶表现出高抗菌活性,因此可以显著增强抗菌处理的功效。由于紫外线照射后形成光二聚Cy-Ag-Cy交联，Ag-Cy-PPG转化为水溶性交联纳米凝胶，具有一系列有趣的化学和物理性质，如强烈和稳定的荧光行为，高度敏感的pH响应特性，开/关可切换相变行为，以及在弱酸性水溶液中银离子（Ag）的控制释放。重要的是,抗菌试验清楚地表明，辐照的Ag-Cy-PPG纳米凝胶在低剂量（MIC值<50μg/mL）下对革兰氏阳性和革兰氏阴性细菌病原体表现出强抗菌活性，而未辐照的Ag-Cy-PPG纳米凝胶不抑制细菌病原体的生存能力。这些结果表明,辐照的Ag-Cy-PPG纳米凝胶由于其相对不稳定的π-共轭结构(与未辐照的纳米凝胶相比)而在细菌微环境中经历高度敏感的结构变化;这种变化导致快速的结构响应,其促进Ag+的细胞内释放并诱导有效的抗菌能力。总的来说,这种新创建的金属-超分子系统可能提供有效的途径来显著提高抗菌治疗的治疗效果.
