Gold-nanoparticles coated with the antimicrobial peptide esculentin-1a (1-21)NH2 as a reliable strategy for antipseudomonal drugs
Gold-nanoparticles coated with the antimicrobial peptide esculentin-1a (1-21)NH2 as a reliable strategy for antipseudomonal drugs
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DOI：
10.1016/j.actbio.2016.09.041
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发表时间：
2017-01-01
影响因子：
9.7
通讯作者：
Mangoni, Maria Luisa
中科院分区：
文献类型：
--
作者：
Casciaro, Bruno;Moros, Maria;Mangoni, Maria Luisa
天然存在的抗菌肽（AMP）有望成为未来针对多药耐药微生物的治疗剂。最近，我们发现蛙皮AMP esculentin-1a的衍生物，ESC（1-21），对自由生活和生物膜形式的细菌病原体铜绿假单胞菌都是非常有效的。然而，将AMP引入临床需要克服其低稳定性、高毒性和在高浓度下低效递送至靶位点。重要的是，肽缀合金纳米粒子（金纳米粒子），这是在生物医学科学中应用最广泛的无机纳米载体之一，代表了一个有价值的策略来解决这些问题。在这里，我们报道了通过聚（乙二醇）接头将ESC（1-21）共价缀合至可溶性AuNP [AuNP @ESC（1-21）]，使游离肽对铜绿假单胞菌的运动和固着形式的活性增加了类似15倍，而对人角质形成细胞没有毒性。此外，AuNPs@ESC（1-21）导致对蛋白水解消化的显著更大抗性，并且在非常低的浓度（5 nM）下分解细菌膜。最后，我们首次证明了肽包被的金纳米颗粒在角质形成细胞单层上显示伤口愈合活性的能力。总体而言，这些发现表明，我们的工程金纳米颗粒可以作为有吸引力的新型生物衍生材料，用于局部治疗上皮感染和愈合的损伤tissue.Statement的SignificanceDespite结合的AMP金纳米颗粒代表了一个值得的解决方案，面对一些限制，他们的发展作为新的疗法，只有非常有限的研究是可用的肽包被的金纳米颗粒。重要的是，这是第一份报告显示，线性AMP通过聚（乙二醇）接头与AuNP的共价结合高度增强了抗假单胞菌活性，保留了游离肽的相同作用模式，而不是有害的。此外，AuNPs@ESC（1-21）预期加速受损皮肤层的恢复。总之，这些发现表明我们的肽包被的AuNP是治疗细菌感染和愈合受伤组织的有吸引力的新型纳米级制剂。(C)2016 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Naturally occurring antimicrobial peptides (AMPs) hold promise as future therapeutics against multidrug resistant microorganisms. Recently, we have discovered that a derivative of the frog skin AMP esculentin-1a, Esc(1-21), is highly potent against both free living and biofilm forms of the bacterial pathogen Pseudomonas aeruginosa. However, bringing AMPs into clinics requires to overcome their low stability, high toxicity and inefficient delivery to the target site at high concentrations. Importantly, peptide conjugation to gold nanoparticles (AuNPs), which are among the most applied inorganic nanocarriers in biomedical sciences, represents a valuable strategy to solve these problems. Here we report that covalent conjugation of Esc(1-21) to soluble AuNPs [AuNPs@Esc(1-21)] via a poly(ethylene glycol) linker increased by similar to 15-fold the activity of the free peptide against the motile and sessile forms of P. aeruginosa without being toxic to human keratinocytes. Furthermore, AuNPs@Esc(1-21) resulted to be significantly more resistant to proteolytic digestion and to disintegrate the bacterial membrane at very low concentration (5 nM). Finally, we demonstrated for the first time the capability of peptide-coated AuNPs to display a wound healing activity on a keratinocytes monolayer. Overall, these findings suggest that our engineered AuNPs can serve as attractive novel biological-derived material for topical treatment of epithelial infections and healing of the injured tissue.Statement of SignificanceDespite conjugation of AMPs to AuNPs represents a worthwhile solution to face some limitations for their development as new therapeutics, only a very limited number of studies is available on peptide-coated AuNPs. Importantly, this is the first report showing that a covalent binding of a linear AMP via a poly (ethylene glycol) linker to AuNPs highly enhances antipseudomonal activity, preserving the same mode of action of the free peptide, without being harmful. Furthermore, AuNPs@Esc(1-21) are expected to accelerate recovery of an injured skin layer. All together, these findings suggest our peptide-coated AuNPs as attractive novel nanoscale formulation to treat bacterial infections and to heal the injured tissue. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.