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光热活性水凝胶装置用于有效释放抗菌肽:按需治疗感染。

Photothermally Active Cryogel Devices for Effective Release of Antimicrobial Peptides: On-Demand Treatment of Infections.

机构信息

Department of Chemistry, Bogazici University, Bebek, Istanbul 34342, Turkey.

Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520-IEMN, Lille F-59000, France.

出版信息

ACS Appl Mater Interfaces. 2020 Dec 23;12(51):56805-56814. doi: 10.1021/acsami.0c17633. Epub 2020 Dec 8.

DOI:10.1021/acsami.0c17633
PMID:33289537
Abstract

There has been significant interest in the use of peptides as antimicrobial agents, and peptide containing hydrogels have been proposed as biological scaffolds for various applications. Limited stability and rapid clearance of small molecular weight peptides pose challenges to their widespread implementation. As a common approach, antibacterial peptides are physically loaded into hydrogel scaffolds, which leads to continuous release through the passive mode with spatial control but provides limited control over drug dosage. Although utilization of peptide covalent linkage onto hydrogels addresses partially this problem, the peptide release is commonly too slow. To alleviate these challenges, in this work, maleimide-modified antimicrobial peptides are covalently conjugated onto furan-based cryogel (CG) scaffolds the Diels-Alder cycloaddition at room temperature. The furan group offers a handle for specific loading of the peptides, thus minimizing passive and burst drug release. The porous nature of the CG matrix provides rapid loading and release of therapeutic peptides, apart from high water uptake. Interfacing the peptide adduct containing a CG matrix with a reduced graphene oxide-modified Kapton substrate allows "on-demand" photothermal heating upon near-infrared (NIR) irradiation. A fabricated photothermal device enables tunable and efficient peptide release through NIR exposure to kill bacteria. Apart from spatial confinement offered by this CG-based bandage, the selective ablation of planktonic is demonstrated. It can be envisioned that this modular "on-demand" peptide-releasing device can be also employed for other topical applications by appropriate choice of therapeutic peptides.

摘要

人们对肽类作为抗菌剂的应用产生了浓厚的兴趣,并且含有肽的水凝胶已被提议作为各种应用的生物支架。由于小分子肽的稳定性有限且清除速度快,因此它们的广泛应用受到了挑战。作为一种常见的方法,抗菌肽被物理加载到水凝胶支架中,通过空间控制以被动模式实现持续释放,但对药物剂量的控制有限。尽管利用肽共价键合到水凝胶上部分解决了这个问题,但肽的释放通常仍然太慢。为了缓解这些挑战,在这项工作中,马来酰亚胺修饰的抗菌肽通过 Diels-Alder 环加成反应在室温下共价连接到呋喃基冷冻凝胶 (CG) 支架上。呋喃基团提供了特定负载肽的方法,从而最大限度地减少了被动和爆发性药物释放。CG 基质的多孔性质除了高吸水性外,还提供了治疗性肽的快速负载和释放。将含有肽加合物的 CG 基质与还原氧化石墨烯修饰的 Kapton 基底相连接,允许在近红外 (NIR) 照射下进行“按需”光热加热。所制造的光热装置能够通过 NIR 暴露实现可调且高效的肽释放,以杀死细菌。除了这种基于 CG 的绷带提供的空间限制外,还证明了对浮游生物的选择性消融。可以想象,通过适当选择治疗性肽,这种模块化的“按需”肽释放装置也可以用于其他局部应用。

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