ADVANCED FUNCTIONAL MATERIALS
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2024
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IF 18.5
Hao Cheng,Yongqiang Yang,Yueyue Wang,Jiqiang Guo,Xiong Jiao,Di Huang,Meiwen An,Xiaohong Yao,Paul K. Chu,Xiangyu Zhang
The hypoxic environment of deep tissue and the weak energy of microwave (MW) are still the major limitations of MW catalytic therapy. In this work, an MW-responsive nano-platform consisting of an Mn-doped porphyrin metal–organic framework loaded with calcium peroxide (Mn 0.1 PCC) is designed to regulate the microenvironment of the injection site and enhance the generation of reactive oxygen species. The excellent MW absorbing properties of Mn 0.1 PCC improve the Fenton reaction between hydrogen peroxide formed by the hydrolysis of calcium peroxide and released Mn 2+ generating more hydroxyl radicals under MW. This process does not consume the oxygen substrate and even produces oxygen to improve the hypoxic environment. Therefore, at a low and safe concentration (125 µg mL −1 ), the antibacterial rate of Mn 0.1 PCC against 4 × 10 8 CFU mL −1 of methicillin-resistant Staphylococcus aureus (MRSA) after MW irradiation for 15 min is 99.71% ± 0.18%. Mn 0.1 PCC, upon exposure to MW, prevents the recurrence of bacterial infections and overcomes drug resistance by inhibiting quorum sensing and the two-component system of MRSA. It can also induce macrophage M1 polarization, up-regulate the pro-inflammatory factor tumor necrosis factor-α, and enhance the phagocytosis of macrophage to bacteria. This strategy provides insights into the development of high-performance MW-responsive nanocomposites for the treatment of infections in deep tissues.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2013
·Vol. 14
·期 1
·1802-1821
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IF 2.464
Rongxin Qin,Kangkang Xiao,Bin Li,Weiwei Jiang,Wei Peng,Jiang Zheng,Hong Zhou
Fructus crataegi (hawthorn) is the common name of all plant species in the genusCrataegusof the Rosaceae family. In the present study, three monomers of (+)-catechin (C), (−)-epicatechin gallate (ECg) and (−)-epigallocatechin (EGC) were isolated from the hawthorn under the guide of antibacterial sensitization activity. The bioactivity of the composite fraction in enhancing the antibacterial effect of oxacillin against methicillin-resistantStaphylococcus aureus(MRSA) was greater than that of the individual monomer of the hawthorn extractin vitro. Two-fold dilution and checkerboard methods were used to analyze antibacterial activity and screen for the combination and proportion of monomers with the best bioactivity. The result showed that C (128 mg/L) combined with ECg (16 mg/L) had the greatest effect and the combination also reduced the bacterial load in blood of septic mice challenged with a sublethal dose of MRSA, increased daunomycin accumulation within MRSA and down-regulated the mRNA expression ofnorA,norCandabcA, three important efflux pumps of MRSA. In summary, C and ECg enhanced the antibacterial effect of β-lactam antibiotics against MRSAin vitroandin vivo, which might be related to the increased accumulation of antibiotics within MRSA via suppression of important efflux pumps’ gene expression.Keywords:fructus crataegi;(+)-catechin;(−)-epicatechin gallate;synergistic effect;MRSA;drug accumulation
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高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Jihui Lu,Zhijia Wang,Desheng Cai,Xiaoyu Lin,Xuemei Huang,Zhihua Yuan,Yaozhi Zhang,Haimin Lei,Penglong Wang
Background Deaths from bacterial infections have risen year by year. This trend is further aggravated as the overuse antibiotics and the bacterial resistance to all known antibacterial agents. Therefore, new therapeutic alternatives are urgently needed.Methods Enlightenment the combination usage of traditional herb medicine, one carrier-free binary nanoparticles (GA-BBR NPs) was discovered, which was self-assembled from gallic acid and berberine through electrostatic interaction, π-π stacking and hydrophobic interaction; and it could be successfully prepared by a green, cost-effective and “one-pot” preparation process.Results The nanoparticles exhibited strong antibacterial activity and biofilm removal ability against multidrug-resistant S. aureus (MRSA) by downregulating mRNA expression of rpsF, rplC, rplN, rplX, rpsC, rpmC and rpsH to block bacterial translation mechanisms in vitro and in vivo, and it had well anti-inflammatory activity and a promising role in promoting angiogenesis to accelerate the wound healing on MRSA-infected wounds model in vivo. Additionally, the nanoparticles displayed well biocompatibility without cytotoxicity, hemolytic activity, and tissue or organ toxicity.Conclusion GA-BBR NPs originated from the drug combination has potential clinical transformation value, and this study provides a new idea for the design of carrier-free nanomedicine derived from natural herbals.
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高影响因子
Pharmaceutics
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2022
·Vol. 14
·期 9
·1937
·
IF 6.525
Chenghua Song,Ruichao Wen,Jiaxuan Zhou,Xiaoyan Zeng,Zi Kou,Jia Zhang,Tao Wang,Pengkang Chang,Yi Lv,Rongqian Wu
The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide,Androctonus amoreuxiAntimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-ResistantStaphylococcus aureus(MRSA) orCandida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.Keywords:antimicrobial peptides;GK-19;skin and soft tissue infections;MRSA;Candida albicans
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ACS Infectious Diseases
·
2024
·
IF 4
Chenchen Wang,Yueyue Ji,Xingyu Huo,Xiaodan Li,Wenjia Lu,Zhaoran Zhang,Wenqi Dong,Xiangru Wang,Huanchun Chen,Chen Tan
Exploring novel antimicrobial drugs and strategies has become essential to the fight MRSA-associated infections. Herein, we found that membrane-disrupted repurposed antibiotic salifungin had excellent bactericidal activity against MRSA, with limited development of drug resistance. Furthermore, adding salifungin effectively decreased the minimum inhibitory concentrations of clinical antibiotics against Staphylococcus aureus. Evaluations of the mechanism demonstrated that salifungin disrupted the level of H+ and K+ ions using hydrophilic and lipophilic groups to interact with bacterial membranes, causing the disruption of bacterial proton motive force followed by impacting on bacterial the function of the respiratory chain and adenosine 5′-triphosphate, thereby inhibiting phosphatidic acid biosynthesis. Moreover, salifungin also significantly inhibited the formation of bacterial biofilms and eliminated established bacterial biofilms by interfering with bacterial membrane potential and inhibiting biofilm-associated gene expression, which was even better than clinical antibiotics. Finally, salifungin exhibited efficacy comparable to or even better than that of vancomycin in the MRSA-infected animal models. In conclusion, these results indicate that salifungin can be a potential drug for treating MRSA-associated infections.
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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ACS Sensors
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2022
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IF 9.618
Yue Xu,Haiyan Chen,Shufen Xu,Ji Liu,Yang Chen,Lijuan Gui,Hua Li,Ruixi Li,Zhenwei Yuan,Bowen Li
Several photosensitizers have recently been proposed as novel approaches against β-lactamase-producing drug-resistant bacteria. However, these reported photosensitizers are rarely used for accurate recognition of drug-resistant bacteria. To tackle this challenge, the structurally modified photosensitizer CySG-2 based on a lipophilic cationic heptamethine indocyanine near-infrared (NIR) dye (IR-780) and an important synthesis intermediate of cephalosporin antibiotic (GCLE) not only achieved the accurate recognition of TEM-1 methicillin-resistant Staphylococcus aureus (MRSA) successfully but also achieved antimicrobial photodynamic therapy (aPDT) in animal models infected by drug-resistant bacteria. Accurate enzyme recognition and efficient photodynamic therapy capabilities allow CySG-2 to achieve one stone with two birds. In addition, CySG-2 could also promote the eradication of internalized MRSA by facilitating the autophagy process, which is synergistic with its capacity of inducing reactive oxygen species generation under NIR laser irradiation for aPDT. Collectively, it is an effective multifunctional photosensitizer with the potential ability to guide the optimal use of different antibiotics and apply them in clinical treatment.
研究领域:
药学
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微生物学
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生物医学工程
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传染病学
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高影响因子
Nanoscale
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2020
·Vol. 12
·期 14
·7651-7659
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IF 6.895
Xujuan Guo,Bing Cao,Congyu Wang,Siyu Lu,Xianglong Hu
Bacterial infection has caused a serious threat to human public health. Methicillin-resistant Staphylococcus aureus (MRSA) is a representative drug-resistant bacterium, which is difficult to eradicate completely, resulting in high infection probability with severe mortality. Herein, pathogen-targeting phototheranostic nanoparticles, Van-OA@PPy, are developed for efficient elimination of MRSA infection. Van-OA@PPy nanoparticles are fabricated from the in situ templated formation of polypyrrole (PPy) in the presence of ferric ions (Fe3+) and a polymer template, hydrophilic poly(2-hydroxyethyl methacrylate-co-N,N-dimethyl acrylamide), P(HEMA-co-DMA). PPy nanoparticles are further coated with vancomycin conjugated oleic acid (Van-OA) to afford the resultant pathogen-targeting Van-OA@PPy. A high photothermal conversion efficiency of ∼49.4% is achieved. MRSA can be efficiently killed due to sufficient nanoparticle adhesion and fusion with MRSA, followed by photothermal therapy upon irradiation with an 808 nm laser. Remarkable membrane damage of MRSA is observed, which contributes greatly to the inhibition of MRSA infection. Furthermore, the nanoparticles have high stability and good biocompatibility without causing any detectable side effects. On the other hand, residual Fe3+ and PPy moieties in Van-OA@PPy endow the nanoparticles with magnetic resonance (MR) imaging and photoacoustic (PA) imaging potency, respectively. The current strategy has the potential to inspire further advances in precise diagnosis and efficient elimination of MRSA infection in biomedicine.
研究领域:
生物医学工程
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纳米技术
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传染病学
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材料科学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 13.2
Yuze Luo,Ying Wang,Cheng Jin,Ke Yang,Zefeng Wang,Yinbang Zheng,Junqin Li,Chunlei Ou,Li Wang,Dinggeng He
The treatment of bacterial wound infection, particularly that caused by methicillin-resistant Staphylococcus aureus (MRSA), presents significant challenges owing to biofilm formation, multidrug resistance, and immune evasion. Here, we have rationally designed a multifunctional composite nanozyme (FTM) consisting of tannic acid (TA) and ferric ion (Fe 3+ ) coordination compound loaded with antibiotic drug methicillin (Meth), which is capable of realizing pH-responsive self-adaptive regulation of oxidative stress for enhancing the treatment of MRSA-infected wound. During the early stages of wound infection (pH < 6.5), FTM demonstrates significant peroxidase-like activity for effectively catalyzing the conversion of endogenous H 2 O 2 into highly toxic hydroxyl radical (•OH), which not only directly damages MRSA and eliminates its biofilm for chemodynamic therapy (CDT), but also disrupts the penicillin-binding protein 2a (PBP2a) to restore the sensitivity of MRSA to methicillin. Meanwhile, FTM exhibits strong near-infrared (NIR) absorption, achieving photothermal antibacterial therapy (PTT). While in the later stages (after complete elimination of MRSA), as the infectious microenvironment of wound becomes neutral (pH 7.4), FTM mainly reveals the superoxide dismutase (SOD)-like activity for scavenging excess reactive oxygen species (ROS), ultimately reducing oxidative stress and promoting tissue repair. In vitro and in vivo experiments show that the proposed FTM nanozyme with triple bactericidal modalities achieves satisfactory antibacterial and antibiofilm therapy and accelerates wound healing process. Consequently, by adapting to the dynamic changes of wound microenvironment, this multifunctional nanoplatform offers a promising strategy for treating drug-resistant wound infections.
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CHEMICAL ENGINEERING JOURNAL
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2022
·
IF 16.744
Luogen Lai,Wanqing Zou,Yan Zhang,Yuanbiao Tu,Simeng Li,Tongxuan Xin,Tianyue Zhou,Shan Xu,Pengwu Zheng,Qingshan Pan,Wufu Zhu
Bacterial infections and antibiotic resistance have become a global healthcare crisis. There is an urgent need to develop visualized therapeutic platforms that allow accurate imaging of the bacterial infections, successful eradication of bacteria and real-time monitoring of treatment progress. In this work, we report a novel NIR imaging and synergistic antibacterial nano-system ( [email protected] ) for resistance bacterial infection therapy. The multifunctional nano-system is fabricated by a MIL-101 core, which is covalently connected with Vancomycin and modified with targeted antimicrobial peptides LL-37 on the surface. The ability of monitoring the progress of infection treatment and effective promoting wound healing of bacterial infection are proved by in vivo MRSA -infected mice models. Under the environment of endogenous H 2 O 2 overexpression and slightly acid bacterial infection, the excellent Fenton-like reaction activity of [email protected] could effectively catalyze the decomposition of H 2 O 2 to produce hydroxyl radicals (•OH), which trigger highly efficient chemo-dynamic therapy (CDT) and tissue protection effect. By combining CDT with antibacterial peptides and antibiotics therapy, special targeting and synergistic killing of MRSA are successfully achieved in in vitro and in vivo antibacterial assays with excellent biocompatibility. Due to this, this study proposes a novel, high-efficient, multifunctional imaging and therapy system, which will open a new avenue for the design of synergistic antibacterial and diagnostic platforms in the future.
研究领域:
纳米技术
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药学
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生物医学工程
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传染病学
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材料科学
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高影响因子
Acta Pharmaceutica Sinica B
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2025
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IF 14.6
Xinxing Li,Wenxin Ding,Yan Lu,Haiyan Zhu,Weilian Bao,Yang Liu,Jiaren Lyu,Lishuang Zhou,Hong Li,Jiyang Li,Daofeng Chen
The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD 50 ) and methicillin-resistant Staphylococcus aureus (MRSA, 10 7 CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut–lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut–lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral–bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.
研究领域:
免疫学
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微生物学
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药理学
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呼吸医学
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高影响因子
Nanomaterials
·
2025
·Vol. 15
·期 14
·1075
·
IF 4.3
Peilin Tian,Xianyue Bai,Jing Feng,Luyao Xu,Shihao Xu,Xiaoya Yu,Caiju Fan,Qian Su,Jiaxing Song,Cuixia Lu
In this study, a pH-responsive nanophotosensitizer (MT@Ce6) was rationally developed by strategic integration of MIL-101 (Fe)-NH 2 metal–organic framework with tannic acid (TA) and chlorin e6. This nanocomposite exhibits pH-responsive degradation in acidic microenvironments, facilitating Fe 3+ release and subsequent reduction to Fe 2+ that catalyzes Fenton reaction-mediated hydroxyl radical (•OH) generation. This cascade reaction shifts reactive oxygen species (ROS) predominance from transient singlet oxygen ( 1 O 2 ) to the long-range penetrative •OH, achieving robust biofilm disruption and over 90% eradication of methicillin-resistant Staphylococcus aureus (MRSA) under 660 nm irradiation. In vivo evaluations revealed accelerated wound healing with 95% wound closure within 7 days, while species-selective antibacterial studies demonstrated a 2.3-fold enhanced potency against Gram-positive bacteria due to their unique peptidoglycan-rich cell wall architecture. These findings collectively establish a microenvironment-adaptive nanoplatform for precision antimicrobial interventions, providing a translational strategy to address drug-resistant infections.
研究领域:
纳米技术
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抗菌治疗
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光动力治疗
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材料科学
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生物医学工程
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高影响因子
Arabian Journal of Chemistry
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2024
·
IF 5.3
Guangyu Pan,Qin Wang,Hangxing Ding,Jianbin Deng,Shiqi Gao,Liping Wang
This study aims to develop new quaternary ammonium salt-based antimicrobial materials with good biocompatibility, biosafety, and strong antimicrobial properties that promote wound healing in infected wounds. First, four new quaternary ammonium salt antibacterial fibers (QASAF) are constructed: QASAF-C12, QASAF-C14, QASAF-C16, and QASAF-C18, with varying carbon chain lengths of C12, C14, C16, and C18, respectively. Then, their structure is characterized by proton nuclear magnetic resonance (NMR) analysis and their hemolytic and cytotoxic properties are also investigated. QASAFs are then evaluated for in vivo and in vitro antimicrobial performance against Staphylococcus aureus ( S. aureus ) and methicillin-resistant Staphylococcus aureus (MRSA). Finally, the effect of QASAF on promoting wound healing in infected wounds is evaluated using mouse wound models infected with S. aureus and MRSA. The obtained results suggest that QASAF is non-toxic to cells in the 25–125 µg/mL concentration range, is slightly hemolytic, has good biocompatibility, and has a biosafety profile. QASAF-C18 shows the best antibacterial performance against S. aureus with significant pro-healing effects on infected wounds. QASAF-C12 exhibits the best antibacterial performance against MRSA with significant pro-healing effects. The novel quaternary ammonium-based antimicrobial material provides a reference for developing antimicrobial and biocompatible wound dressings.
研究领域:
材料科学
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生物医学工程
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药学
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微生物学
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危险品化学品经营许可证（带存储）