Gram-selective antibacterial peptide hydrogels

Hou, Yangqian; Tan, Tingyuan; Guo, Zhen; Zhang, Lijuan; Hu, Jun; Zhang, Yi

doi:10.1039/d2bm00558a

Cited by 19 publications

(26 citation statements)

References 90 publications

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Section: Resultssupporting

confidence: 89%

“…S. aureus without any treatment of the sample was considered as a negative control, and gentamycin sulfate was taken as a positive control. The activity against S. aureus is similar to the activity reported by Cao et al, 49 Hou et al, 50 Gahane et al, 51 and Bai et al 52 Live/dead cell staining of S. aureus treated with gels was carried out with SYTO 9 and PI (Figure 4D). Bacteria were treated with gels for 12 h, and the staining solution was added followed by the incubation.…”

Section: ■ Results and Discussionsupporting

confidence: 84%

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Supramolecular, Nanostructured Assembly of Antioxidant and Antibacterial Peptides Conjugated to Naproxen and Indomethacin for the Selective Inhibition of COX-2, Biofilm, and Inflammation in Chronic Wounds

2023

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Chronic wounds are a major healthcare challenge around the world. The presence of bacterial biofilms, accumulation of reactive oxygen species (ROS), and persistent inflammation have been identified as rate-limiting steps in chronic wound healing. Anti-inflammatory drugs, like naproxen (Npx) and indomethacin (Ind), show poor selectivity for the COX-2 enzyme, which plays a key role in producing inflammatory responses. To address these challenges, we have developed conjugates of Npx and Ind with peptides possessing antibacterial, antibiofilm, and antioxidant properties along with enhanced selectivity for the COX-2 enzyme. We have synthesized and characterized peptide conjugates Npx-YYk, Npx-YYr, Ind-YYk, and Ind-YYr, which were self-assembled into supramolecular gels. As envisaged, the conjugates and gels showed high proteolytic stability and selectivity toward the COX-2 enzyme and potent antibacterial activities (>95% within 12 h) against Gram-positive bacteria Staphylococcus aureus, implicated in wound-related infections, eradication of biofilm (∼80%), and radical scavenging (>90%) properties. Cell culture studies with mouse fibroblast cells (L929) and macrophage-like cells (RAW 264.7) showed that gels were cell proliferative in nature (120% viability), which resulted in faster and more efficient scratch healing. Treatment with gels led to a significant decrease in proinflammatory cytokine (TNF-α and IL-6) expressions and an increase in anti-inflammatory gene (IL-10) expression. The gels developed in this work show great promise as a topical agent for chronic wounds or as a coating for medical devices to prevent medical-device-associated infections.

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Section: Resultssupporting

confidence: 89%

Section: ■ Results and Discussionsupporting

confidence: 84%

Supramolecular, Nanostructured Assembly of Antioxidant and Antibacterial Peptides Conjugated to Naproxen and Indomethacin for the Selective Inhibition of COX-2, Biofilm, and Inflammation in Chronic Wounds

2023

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“…In addition, the N-terminus of the peptide motif FIIIKKK was modified to include hydrophobic groups naphthalene (Nap) and phloretic acid [3-(4-hydroxyphenyl) propionic acid] for the construction of the ACPs/AMPs IK1 and IK3, respectively, to promote peptide self-assembly (Figure a). The antibacterial activities of the IK1 and IK3 peptides and their efficacy as antibacterial hydrogel dressings have been thoroughly examined in our previously published work …”

Section: Resultsmentioning

confidence: 99%

“…We think that DN hydrogels , composed of polyvinyl alcohol (PVA) and ACPs may be particularly suitable to enhance the ACP hydrogels’ strength and toughness for biomedical use, as PVA is biocompatible and has little effect on the peptides’ characteristics such as assembly property and antitumor/antibacterial ability. , In this research, we have constructed ACP/PVA-based DN hydrogels for the direct treatment of melanoma. It was found that our previously developed AMPs, IK1 and IK3, which have excellent antibacterial properties, specifically target mouse melanoma cells B16-F10 while being nontoxic to healthy cells. IK1/PVA and IK3/PVA DN hydrogels were created.…”

Section: Introductionmentioning

confidence: 99%

Peptide-Based Double-Network Hydrogels for Melanoma Treatment and Wound Healing Promotion

Hou

Tian

et al. 2023

ACS Appl. Mater. Interfaces

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Although surgery is the primary method to treat malignant melanoma, it has drawbacks such as residual tumor that could trigger cancer recurrence and wound infections that are especially difficult to heal in diabetics. In this research, we have constructed anti-cancer peptides/polyvinyl alcohol (PVA) doublenetwork (DN) hydrogels for the treatment of melanoma. The maximum stress of the DN hydrogels is found to be larger than 2 MPa, which endows the DN hydrogels with ideal mechanical performance for therapeutic wound dressing. The peptides naphthalene-FIIIKKK (IK1) and phloretic acid-FIIIKKK (IK3) that were previously developed as effective antibacterial peptides, as well as the peptide/PVA DN hydrogels, are found to have good anti-cancer efficacy and target mouse melanoma cells B16-F10 while being nontoxic to normal cells. Further studies have revealed that IK1 and IK3 damage the tumor cell membrane and mitochondrial membrane and eventually trigger apoptosis. In the mouse melanoma model and the diabetic bacterial infection model, the DN hydrogels exhibit great anti-tumor, anti-bacterial, and wound healing promotion abilities in vivo. Because of their excellent mechanical properties, the DN hydrogels are promising soft materials for directly treating malignant melanomas as well as for preventing recurrence and bacterial infection after melanoma surgery that promote wound healing.

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“…Current strategies that are generally based on the cell membrane differences, such as membrane charge and sugar composition, have successfully achieved the antibacterial selectivity for Gram-positive or Gram-negative bacteria . Alternative strategies of selective antibacterial activity involve regulating the chemical structure of antibacterial agents, such as charges, hydrophobicity, and functions. − For example, Tang’s group achieved the selectivity to Gram-positive bacteria by increasing the positive charges of amphiphiles . Banerjee’s group extended the alkyl chain to enhance the hydrophobicity of nanoparticles (NPs), and these amphiphiles displayed selectivity to Gram-negative bacteria .…”

mentioning

confidence: 99%

Phospholipid-Mimetic Aggregation-Induced Emission Luminogens for Specific Elimination of Gram-Positive and Gram-Negative Bacteria

Shen

Wang

et al. 2023

ACS Nano

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Precise elimination of both Gram-positive and Gram-negative bacteria greatly contributes to the fight against bacterial infection but remains challenging. Herein, we present a series of phospholipid-mimetic aggregation-induced emission luminogens (AIEgens) that selectively kill bacteria by capitalizing on both the different structure of two bacterial membrane and the regulated length of substituted alkyl chains of AIEgens. Because of the positive charges that they contain, these AIEgens are able to kill bacteria by anchoring onto the bacterial membrane. For AIEgens with short alkyl chains, they could combine with the membrane of Gram-positive bacteria other than Gram-negative bacteria, because of their complicated outer layers, thus exhibiting selective ablation to Gram-positive bacteria. On the other hand, AIEgens with long alkyl chains have strong hydrophobicity with bacterial membranes, as well as large sizes. This inhibits the combination with Gram-positive bacterial membrane but destroys the membranes of Gram-negative bacteria, resulting in selective ablation to Gram-negative bacteria. Moreover, the combined processes to two bacteria are clearly observed by fluorescent imaging, and in vitro and in vivo experiments show the extraordinary antibacterial selectivity toward a Gram-positive and Gram-negative bacterium. This work could facilitate the development of species-specific antibacterial agents.

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Gram-selective antibacterial peptide hydrogels

Abstract: Human microbiome has fundamental roles in human health and disease. However, the widely used broad-spectrum antibiotics severely disrupt human-related microbial communities, eventually leading to resistant bacteria and posing a growing...

Cited by 19 publications

References 90 publications

Supramolecular, Nanostructured Assembly of Antioxidant and Antibacterial Peptides Conjugated to Naproxen and Indomethacin for the Selective Inhibition of COX-2, Biofilm, and Inflammation in Chronic Wounds

Supramolecular, Nanostructured Assembly of Antioxidant and Antibacterial Peptides Conjugated to Naproxen and Indomethacin for the Selective Inhibition of COX-2, Biofilm, and Inflammation in Chronic Wounds

Peptide-Based Double-Network Hydrogels for Melanoma Treatment and Wound Healing Promotion

Phospholipid-Mimetic Aggregation-Induced Emission Luminogens for Specific Elimination of Gram-Positive and Gram-Negative Bacteria

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