Alkaline-responsive polydiacetylene-peptide hydrogel for pH-sensing and on-demand antimicrobial release
Alkaline-responsive polydiacetylene-peptide hydrogel for pH-sensing and on-demand antimicrobial release
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DOI：
10.1016/j.mtadv.2022.100288
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发表时间：
2022-12
影响因子：
10
通讯作者：
Weike Chen;Shan Hazoor;R. Madigan;Ashley A. Adones;Uday Chintapula;K. Nguyen;Liping Tang;F. Foss;He Dong
中科院分区：
文献类型：
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作者：
Weike Chen;Shan Hazoor;R. Madigan;Ashley A. Adones;Uday Chintapula;K. Nguyen;Liping Tang;F. Foss;He Dong
抗生素耐药性是一个全球性的公共卫生问题，抗生素的滥用和过度使用加速了这一问题。微环境靶向抗菌素递送是一种新兴的、有前途的选择性抗生素递送策略，它可以靶向感染部位，并可能减少耐药性。感染组织的局部pH值可以成为设计具有pH触发抗菌活性的材料的主要目标。鉴于迫切需要对抗细菌感染的疾病与pH升高，我们报告了一种新的碱反应抗菌水凝胶的设计和合成。该凝胶基于聚二乙基肽（PDA-Pep），具有ph依赖性的分子和大分子结构和包装。当pH值升高时，肽结构域去质子化并触发PDA结构域的构象变化，导致从蓝色到紫色的比色转变。同时，去质子化诱导了PDA-Pep水凝胶中形成的纤维网络从凝胶到溶胶的宏观相变，导致包裹在凝胶中的抗菌药物选择性释放到感染部位杀死细菌。在接种的猪皮上证明了PDA-Pep水凝胶在ph感应和按需碱触发抗生素递送方面的翻译潜力。这项工作为开发多功能碱反应材料奠定了基础，其中可以封装多种小分子或大分子治疗药物，以实现针对多种多重耐药病原体的协同生物学功能。
Antibiotic resistance is a global public health issue, accelerated by the misuse and overuse of antibiotics. Microenvironment-targeted antimicrobial delivery is an emergent and promising strategy for selective antibiotic delivery that targets the site of infections and may reduce drug resistance. The local pH of infected tissues can be a primary target for designing materials with pH-triggered antimicrobial activity. Given the urgent need to combat bacterial infections in diseases with an elevated pH, we report on the design and synthesis of a new alkaline-responsive antimicrobial hydrogel. The gels are based on a polydiacetylene-peptide (PDA-Pep) having pH-dependent molecular and macromolecular structure and packing. Upon pH elevation, the peptide domain is deprotonated and triggers the conformational change of the PDA domain, leading to a colorimetric transition from blue to purple. Simultaneously, the deprotonation induces a gel-to-sol macroscopic phase transition of the fiber network formed in PDA-Pep hydrogels, which causes the selective release of the antimicrobial agents that are encapsulated in the gels into the infection site to kill bacteria. The translational potential of PDA-Pep hydrogels for pH-sensing and on-demand alkaline-triggered antibiotic delivery was demonstrated on inoculated pig skins. The work lays the foundation for the development of multifunctional alkaline-responsive materials in which multiple small molecule or macromolecular therapeutics can be encapsulated to achieve synergistic biological functions against a wide range of multidrug-resistant pathogens.