Self-assembling ultrashort NSAID-peptide nanosponges: multifunctional antimicrobial and anti-inflammatory materials
Self-assembling ultrashort NSAID-peptide nanosponges: multifunctional antimicrobial and anti-inflammatory materials
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DOI：
10.1039/c6ra20282a
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发表时间：
2016-01-01
期刊：
影响因子：
3.9
通讯作者：
Laverty, G.
中科院分区：
文献类型：
--
作者：
McCloskey, A. P.;Gilmore, S. M.;Laverty, G.
基于肽的材料由于其高度的化学和功能通用性而在生物医学中的使用中受到显著关注，使得能够定制其结构以复制宿主组织和细胞外基质的性质。本文研究了非甾体抗炎药-肽偶联物的设计、合成和表征。NSAID与二苯丙氨酸-二赖氨酸（FFKK-OH）肽序列的连接产生具有抗微生物和抗炎性质的超分子水凝胶形成分子。NSAID-肽表现出针对革兰氏阳性和革兰氏阴性细菌的广谱抗微生物活性，所述革兰氏阳性和革兰氏阴性细菌涉及多种抗微生物剂抗性医院感染，包括金黄色葡萄球菌和铜绿假单胞菌。萘普生-肽显示出特别的前景，形成生物相容性纳米纤维粘弹性水凝胶纳米海绵，其由低浓度（0.4%w/v）的β-折叠二级结构组成。肽基序FFKK-OH与萘普生的缀合增加了对考克斯-2酶的选择性，该酶与慢性伤口瘢痕组织形成有关。我们的研究结果表明，超短NSAID肽具有潜在的用途，作为一系列生物医学应用的多功能材料。这包括作为用于治疗慢性伤口的局部药剂，其中已证明持续性炎症、疼痛和感染的存在对成功的伤口修复是有害的。这项工作也可以作为未来医疗器械涂层设计的模板，具有定制的抗菌和抗炎性能。
Peptide-based materials are receiving significant attention for use within biomedicine due to their high chemical and functional versatility enabling tailoring of their structure to replicate the properties of host tissue and the extracellular matrix. This paper studies the design, synthesis and characterization of NSAID-peptide conjugates. Attachment of NSAIDs to a diphenylalanine-dilysine (FFKK-OH) peptide sequence generates supramolecular hydrogel forming molecules with antimicrobial and anti-inflammatory properties. NSAID-peptides demonstrate broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria implicated in a variety of antimicrobial resistant nosocomial infections including Staphylococcus aureus and Pseudomonas aeruginosa. Naproxen-peptides show particular promise, forming biocompatible nanofibrous viscoelastic hydrogel nanosponges composed of beta-sheet secondary structures at low concentrations (0.4% w/v). Conjugation of the peptide motif FFKK-OH to naproxen increases selectivity for COX-2 enzyme, implicated in chronic wound scar-tissue formation. Our findings suggest that ultrashort NSAID-peptides have potential use as multifunctional materials for a range of biomedical applications. This includes as topical agents for treatment of chronic wounds, where a profile of persistent inflammation, pain and the presence of infection has been proven to be detrimental to successful wound repair. This work may also serve as a template for the design of future medical device coatings with tailored antimicrobial and anti-inflammatory properties.