ACS Applied Materials & Interfaces
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2021
·
IF 9.229
Yao Jin,Yudong Yang,Wei Duan,Xuetong Qu,Jianmin Wu
Due to the abuse of antibiotics, antimicrobial resistance is rapidly emerging and becoming a major global risk for public health. Thus, there is an urgent need for reducing the use of antibiotics, finding novel treatment approaches, and developing controllable release systems. In this work, a dual synergistic antibacterial platform with on-demand release ability based on silver nanoparticles (AgNPs) and antimicrobial peptide (AMP) coloaded porous silicon (PSi) was developed. The combination of AgNPs and AMPs (Tet-213, KRWWKWWRRC) exhibited an excellent synergistic antibacterial effect. As a carrier, porous silicon can efficiently load AgNPs and AMP under mild conditions and give the platform an on-demand release ability and a synergistic release effect. The AgNPs and AMP coloaded porous silicon microparticles (AgNPs-AMP@PSiMPs) exhibited an acid pH and reactive oxygen species (ROS)-stimulated release of silver ions (Ag+) and AMPs under bacterial infection conditions because of oxidation and desorption effects. Moreover, the release of the bactericide could be promoted by each other due to the interplay between AgNPs and Tet-213. In vitro antibacterial tests demonstrated that AgNPs-AMP@PSiMPs inherited the intrinsic properties and synergistic antibacterial efficiency of both bactericides. In addition, wound dressing loaded with AgNPs-AMP@PSiMPs showed outstanding in vivo bacteria-killing activity, accelerating wound-healing, and low biotoxicity in aStaphylococcus aureus-infected rat wound model. The present work demonstrated that PSiMPS might be an efficient platform for loading the antibiotic-free bactericide, which could synergistically and on-demand release to fight wound infection and promote wound healing.
研究领域:
药学
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材料科学
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生物医学工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 9
·3214-3226
·
IF 6.6
Haijun Fu,Jiayu Yang,Zongshan Shen,Yong Zhang,Shuhong Kuang,Lifeng Li,Zhengmei Lin,Xuetao Shi
The severe pain caused by oral ulcers seriously affects food intake and speech, bringing great inconvenience in daily life. Drug-loaded patches are mostly used to treat oral mucosal diseases such as oral ulcers and oral lichen planus, but their effects are limited because of the influences of saliva and muscle movement. To enhance the adhesion of drug-loaded patches used in the oral cavity, we designed antimicrobial peptides (AMPs)-modified polycaprolactone (PCL)–collagen nanosheets (APCNs). The internal layer is a bioactive and antibacterial collagen layer modified with antimicrobial peptides. The backing layer is a hydrophobic PCL layer with good mechanical strength that can reduce external influences. We have characterized and tested the APCNs. First, the APCNs exhibited continuous and strong adhesion to irregular buccal mucosa surfaces under wet conditions and external force action. Antibacterial experiments showed that the APCNs had high antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. Moreover, the APCNs showed good biocompatibility and promoted the adhesion of fibroblasts in vitro. Furthermore, APCNs treatment accelerated ulcer healing in a Sprague Dawley rat oral ulcer model. Our study developed antibacterial, wet-adhesive, and healing-promoting PCL-collagen nanosheets and demonstrated that these nanosheets could be promising adhesive therapeutic agents for the treatment of oral mucosal ulcers.
研究领域:
药学
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材料科学
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生物医学工程
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牙科
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组织工程
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 17
·2111344
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IF 19.924
Kaicheng Tang,Xiaoyou Wang,Miaomiao Niu,Xinyu Wang,Guanghua Zhou,Jinjin Shi,Yang Yu,Zhangbao Chen,Chong Li
Antimicrobial peptides (AMPs) have aroused extensive attention due to their low incidences of resistance, yet their clinical transformation is thwarted by inferior selectivity and metabolic stability concerns, manifesting as rapid degradation, off-target, and non-selective toxicity. Here, a captivating affinity-filtering strategy is proposed as a feasible solution for such challenges. Specifically, based on the selective affinity of AMPs toward distinct phospholipids, the membrane of host cells (e.g., erythrocytes) is pre-bound to AMPs as the “filter,” which could screen out off-target substances with non-specific affinity while maintaining effective interaction with high-affinity pathogens through competitive binding, realizing precise targeting, and enhanced stability. The practicability of the affinity-filtering strategy has been demonstrated both in vitro and in vivo, through systematic studies on various AMPs and AMPs-modified delivery systems with multiple fungal infection models ( Candida albicans and Cryptococcus neoformans ), which pose severe threats to human health worldwide yet are often neglected. AMP-modified nanoparticles with affinity filtering exhibit reduced off-target toxicity, sufficient binding with target pathogen, as well as a substantially elevated 21-day survival rate from 30% (conventional drug-loaded nanoparticles) to 70%. In summary, this strategy may provide inspiration for overcoming off-target effects in drug targeting and further promote the clinical application of AMPs.
研究领域:
药学
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微生物学
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药物递送系统
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传染病学
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DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
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2022
·Vol. 41
·期 3
·345-355
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IF 3.815
Liu Hui,Liu Xiao,Cao Yuan-Qiao,Liu Ming,Han Miao-Miao,Ji Sheng-Xiang
Antimicrobial peptides (AMPs) have been considered as an alternative to small molecule antibiotics since they are difficult to develop antimicrobial resistance. Hyperbranched polylysine (HPL), an AMP mimics, has gained attention due to its broad-spectrum antibacterial activities, but it also suffers from high toxicity. Here we report a facile strategy to engineer the toxicity of HPL by copolymerizing lysine (K) with a hydrophobic amino acid, e.g. , alanine (A), tryptophan (W) or phenylalanine (F), to afford hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and in vivo toxicities are lowered when the type and content of hydrophobic amino acid and the size of copolymers are optimized. The G. mellonella infection model demonstrates that the copolymers are effective against the S. aureus infection in vivo . The copolymers kill the bacteria through the disruption of cell membranes and the bacteria do not develop resistance to the copolymers.
研究领域:
材料科学
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生物医学工程
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微生物学
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药学
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产品关联
DOI
高影响因子
MOLECULES
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2024
·Vol. 29
·期 7
·1534
·
IF 4.2
Zhizhi Chen,Lei Wang,Dongxia He,Qi Liu,Qinqin Han,Jinyang Zhang,A-Mei Zhang,Yuzhu Song
Antibiotic resistance has emerged as a grave threat to global public health, leading to an increasing number of treatment failures. Antimicrobial peptides (AMPs) are widely regarded as potential substitutes for traditional antibiotics since they are less likely to induce resistance when used. A novel AMP named Brevinin-1BW (FLPLLAGLAASFLPTIFCKISRKC) was obtained by the Research Center of Molecular Medicine of Yunnan Province from the skin of thePelophylax nigromaculatus. Brevinia-1BW had effective inhibitory effects on Gram-positive bacteria, with a minimum inhibitory concentration (MIC) of 3.125 μg/mL againstEnterococcus faecalis(ATCC 29212) and 6.25 μg/mL against bothStaphylococcus aureus(ATCC 25923) and multidrug-resistantStaphylococcus aureus(ATCC 29213) but had weaker inhibitory effects on Gram-negative bacteria, with a MIC of ≥100 μg/mL. Studies using scanning electron microscopy (SEM) and flow cytometry have revealed that it exerts its antibacterial activity by disrupting bacterial membranes. Additionally, it possesses strong biofilm inhibitory and eradication activities as well as significant lipopolysaccharide (LPS)-binding activity. Furthermore, Brevinin-1BW has shown a significant anti-inflammatory effect in LPS-treated RAW264.7 cells. In conclusion, Brevinin-1BW is anticipated to be a promising clinical agent with potent anti-Gram-positive bacterial and anti-inflammatory properties.
研究领域:
微生物学
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药理学
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传染病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 10
·期 3
·834-845
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IF 6.843
Xiaodan Wang,Fangping Yang,Huawei Yang,Xu Zhang,Haoyu Tang,Shifang Luan
Antimicrobial peptides (AMPs) are attractive antimicrobial agents used to combat bacterial infections, and have been advanced to be one of the most promising alternatives to conventional antibiotics. They stand out for their attractive broad-spectrum activity, unmatched antibacterial mechanism that is not prone to develop drug resistance and diversified topologies, which can be fabricated with manifold amino acid blocks. In this study, using n-hexylamine and amine-terminated polyamidoamine dendrimers (Gx-PAMAM, x = 1–2) as initiators, a series of AMPs with linear and star-shaped topological structures were constructed via the controllable ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs). The antibacterial performances of the tailored linear and star-shaped AMPs were comprehensively evaluated in both solution states and surface-bonded states. The results indicated that the star-shaped AMPs exhibited enhanced bactericidal activity against Gram-negative E. coli and similar bactericidal activity against Gram-positive S. aureus when compared with the linear AMPs. It is worth mentioning that star-shaped AMPs demonstrated a significantly faster bactericidal efficiency (completely killed bacteria within 5 min at a concentration of 2 × MIC for S. aureus) than their linear analogues (took 15 min to achieve the same effect). However, when the AMPs were immobilized to the surface, they similarly exhibited superior antibacterial activity and fast bactericidal efficiency towards S. aureus and E. coli in the case of the same surface grafting amount. In addition, both the surfaces grafted with AMPs of different topologies demonstrated favorable biocompatibility in vitro.
研究领域:
生物材料
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生物技术
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微生物学
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高分子化学
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产品关联
DOI
PubMed
高影响因子
Insect Science
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2024
·
IF 2.9
Wen-Xuan Qi,Feng Liu,Fang-Fang Liu,Hai-Yan Ren,Bang-Xian Zhang,Xiao-Qiang Yu,Xiang-Jun Rao
Antimicrobial peptides (AMPs) are critical components of innate immunity in diverse organisms, including plants, vertebrates, and insects. This study identified and characterized a novel Lepidoptera-specific AMP, named lepidoptin, from the invasive pest Spodoptera frugiperda (Lepidoptera: Noctuidae). Lepidoptin is a 116-amino acid protein containing a signal peptide and a novel β -sandwich domain that is distinct from previously reported AMPs. Temporal and spatial expression analyses revealed a significant upregulation of the lepidoptin gene in vivo and in cultured SF9 cells in response to pathogens. Molecular docking analysis identified a specific binding cavity. Enzyme-linked immunosorbent assay and binding assays confirmed that lepidoptin can bind to pathogen-associated molecular patterns, bacteria, and fungi. Recombinant lepidoptin exhibited potent antibacterial activity by inducing bacterial agglutination, inhibiting bacterial growth, increasing bacterial membrane permeability, and preventing biofilm formation. Lepidoptin also showed antifungal activity against the entomopathogenic fungus Beauveria bassiana by inhibiting spore germination, increasing fungal cell permeability, and increasing reactive oxygen species. Injection of recombinant lepidoptin into S. frugiperda larvae increased survival after B. bassiana infection, whereas knockdown of lepidoptin by RNA interference decreased larval survival. In addition, lepidoptin showed antimicrobial activity against the plant pathogen Fusarium graminearum by inhibiting spore germination and alleviating disease symptoms in wheat seedlings and cherry tomatoes. This study demonstrates the remarkable dual functionality of lepidoptin in enhancing S. frugiperda immunity and controlling plant pathogens, making it a promising candidate for biocontrol strategies in both pest management and plant disease prevention.
研究领域:
昆虫学
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微生物学
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分子生物学
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植物病理学
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害虫管理
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生物防治
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-26
·
IF 14.7
Ye Zifan,Fu Lei,Li Shuangyu,Chen Ziying,Ouyang Jianhong,Shang Xinci,Liu Yanli,Gao Lianghui,Wang Yipeng
Non-direct antimicrobial cationic peptides (NDACPs) are components of the animal innate immune system. But their functions and association with antimicrobial peptides (AMPs) are incompletely understood. Here, we reveal a synergistic interaction between the AMP AW1 and the NDACP AW2, which are co-expressed in the frog Amolops wuyiensis . AW2 enhances the antibacterial activity of AW1 both in vitro and in vivo, while mitigating the development of bacterial resistance and eradicating biofilms. AW1 and AW2 synergistically damage bacterial membranes, facilitating cellular uptake and interaction of AW2 with the intracellular target bacterial genomic DNA. Simultaneously, they trigger the generation of ROS in bacteria, contributing to cell death upon reaching a threshold level. Moreover, we demonstrate that this synergistic antibacterial effect between AMPs and NDACPs is prevalent across diverse animal species. These findings unveil a robust and previously unknown correlation between AMPs and NDACPs as a widespread antibacterial immune defense strategy in animals.
研究领域:
免疫学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2021
·
IF 5.64
Wang Zhihua,Li Qiuke,Li Jinze,Li Jiawei,Shang Lu,Chou Shuli,Lyu Yinfeng,Shan Anshan
Antibiotic resistance is emerging as a hot issue with the abuse and overuse of antibiotics, and the shortage of effective antimicrobial agents against multidrug resistant bacteria creates a huge problem to treat the threatening nosocomial skin and soft tissue infection. Antimicrobial peptides (AMPs) exhibite enormous potential as one of the most promising candidates of antibiotic to fight against pathogenic infections because of its unique membrane penetration mechanism to kill pathogens, whereas the clinical application of AMPs still faces the challenges of production cost, stability, safety, and design strategy. Herein, a series of Trp-rich peptides was designed following the principle of paired Trp plated at the ith and ith+4 position on the backbone of peptides, based on the template (VKKX)4, where X represents W, A, or L, to study the effect of intramolecular aromatic interactions on the bioactivity of AMPs. Through comparing the antimicrobial performance, hemolysis, cytotoxicity, and stability, VW5 which is equipped with the characters of direct antimicrobial efficacy (GM=1.68μM) and physical destruction of bacterial membrane (SEM and electron microscopy) stood out from the engineering peptides. VW5 also performed well in mice models, which could significantly decrease the bacterial colony (VW5 vs infection group, 12.72±2.26 vs 5.52±2.01×109CFU/abscess), the area of dermo-necrosis (VW5 vs infection group, 0.74±0.29 vs 1.86±0.98mm2) and the inflammation cytokine levels at the abscess site without causing toxicity to the skin. Overall, this study provides a strategy and template to diminish the randomness in the exploration and design of novel peptides.
研究领域:
药理学
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微生物学
·
传染病学
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分子生物学
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生物技术
✓ 已验证
DOI
PubMed
高影响因子
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