Antimicrobial peptide shows enhanced activity and reduced toxicity upon grafting to chitosan polymers

Sahariah, Priyanka; Sørensen, Kasper K.; Hjálmarsdóttir, Martha Á.; Sigurjónsson, Ólafur E.; Jensen, Knud J.; Másson, Már; Thygesen, Mikkel B.

doi:10.1039/c5cc04010h

Cited by 96 publications

(89 citation statements)

References 32 publications

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“…Monoclonal antibody and antibacterial peptide have been demonstrated as effective bacteria recognition systems via surface antigen binding or electrostatic interaction . However, high cost and fast body clearance are impeding the development of specific recognition and bacteria killing in vivo based on antigen and peptide . In this regard, effortless and reliable strategies are highly desirable to identify and kill infection‐causing bacterial strains.…”

Section: Methodsmentioning

confidence: 99%

Metal–Organic‐Framework‐Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy

et al. 2018

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Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through noninvasive theranostic approaches. Herein, a new strategy is reported to achieve in vivo metabolic labeling of bacteria through the use of MIL-100 (Fe) nanoparticles (NPs) as the nanocarrier for precise delivery of 3-azido-d-alanine (d-AzAla). After intravenous injection, MIL-100 (Fe) NPs can accumulate preferentially and degrade rapidly within the high H O inflammatory environment, releasing d-AzAla in the process. d-AzAla is selectively integrated into the cell walls of bacteria, which is confirmed by fluorescence signals from clickable DBCO-Cy5. Ultrasmall photosensitizer NPs with aggregation-induced emission characteristics are subsequently designed to react with the modified bacteria through in vivo click chemistry. Through photodynamic therapy, the amount of bacteria on the infected tissue can be significantly reduced. Overall, this study demonstrates the advantages of metal-organic-framework-assisted bacteria metabolic labeling strategy for precise bacterial detection and therapy guided by fluorescence imaging.

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Section: Methodsmentioning

confidence: 99%

Metal–Organic‐Framework‐Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy

et al. 2018

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“…Chitosan ( Figure 8 b) is a linear biocompatible, biodegradable carbohydrate polymer with some antimicrobial activity [ 173 ]. Conjugation of the short and moderately active anolin to chitosan increased the antimicrobial activity of the conjugate and abolished the hemolytic activity [ 174 ]. In general, the antimicrobial activity increased in proportion to the number of peptides attached to the chitosan polymer.…”

Section: Strategies To Improve Antimicrobial Peptidesmentioning

confidence: 99%

Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo

2018

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Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads bacteria to develop no or low resistance. In this review, we discuss the diversity, history and the various mechanisms of action of AMPs. Although many AMPs have reached clinical trials, to date not many have been approved by the US Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage and short half-life. Some of the recent strategies developed to improve the activity and biocompatibility of AMPs, such as chemical modifications and the use of delivery systems, are also reviewed in this article.

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“…Furthermore, it itself displays mild antibacterial properties against a broad spectrum of microorganisms, which can be tuned by molecular weight and chemical modification via amine groups (e.g., deacetylation) [ 79 ]; as such, it has gained some attention as a promising delivery vehicle for AMPs. Much work has been published detailing the utilization of chitosan to improve the biocompatibility of peptides while maintaining or enhancing their antimicrobial activity [ 79 , 133 , 134 , 135 , 136 ]. For example, Hou et al developed self-assembled short chain chitosan-polylysine AMP nanoparticles that displayed strong broad-spectrum activity both in vitro and in vivo with very low hemolytic activity and improved selectivity [ 136 ].…”

Section: Delivery Vehiclesmentioning

confidence: 99%

Towards Robust Delivery of Antimicrobial Peptides to Combat Bacterial Resistance

2020

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Antimicrobial peptides (AMPs), otherwise known as host defence peptides (HDPs), are naturally occurring biomolecules expressed by a large array of species across the phylogenetic kingdoms. They have great potential to combat microbial infections by directly killing or inhibiting bacterial activity and/or by modulating the immune response of the host. Due to their multimodal properties, broad spectrum activity, and minimal resistance generation, these peptides have emerged as a promising response to the rapidly concerning problem of multidrug resistance (MDR). However, their therapeutic efficacy is limited by a number of factors, including rapid degradation, systemic toxicity, and low bioavailability. As such, many strategies have been developed to mitigate these limitations, such as peptide modification and delivery vehicle conjugation/encapsulation. Oftentimes, however, particularly in the case of the latter, this can hinder the activity of the parent AMP. Here, we review current delivery strategies used for AMP formulation, focusing on methodologies utilized for targeted infection site release of AMPs. This specificity unites the improved biocompatibility of the delivery vehicle with the unhindered activity of the free AMP, providing a promising means to effectively translate AMP therapy into clinical practice.

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Antimicrobial peptide shows enhanced activity and reduced toxicity upon grafting to chitosan polymers

Cited by 96 publications

References 32 publications

Metal–Organic‐Framework‐Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy

Metal–Organic‐Framework‐Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy

Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo

Towards Robust Delivery of Antimicrobial Peptides to Combat Bacterial Resistance

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