JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-20
·
IF 10.435
Xu Shibo,Chang Linna,Hu Yanan,Zhao Xingjun,Huang Shuocheng,Chen Zhenhua,Ren Xiuli,Mei Xifan
Background Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant.Results The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats.Conclusion sThe obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics.Graphical Abstract
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高影响因子
Small
·
2021
·Vol. 18
·期 10
·2107137
·
IF 13.281
Guangxin Duan,Ling Wen,Xingwei Sun,Zhuxin Wei,Ruixue Duan,Jiangfeng Zeng,Jiabin Cui,Chunyi Liu,Zepeng Yu,Xiaofang Xie,Mingyuan Gao
Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long-term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO 3− X ) for healing the DUs are reported. The ROS scavenging ability of MoO 3− X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO 3− X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus , manifesting the potent application prospect of MoO 3− X nanodots for diabetic wound therapy.
研究领域:
纳米技术
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材料科学
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生物医学工程
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药学
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伤口护理
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高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Yayun Jiang,Zongyao Chen,Xiao Liu,Qi Xin,Dengchao Wang,Caixia Ji,Youwei Li,Gang Mai
Methicillin-resistant Staphylococcus aureus (MRSA), a widely drug-resistant bacterium, poses a significant threat to global health. Current culturing and nucleic acid detection methods are time-consuming and require complex instruments, which do not meet the detection needs. Herein, we developed a rapid and visual MRSA detection method (MCFHCR) using ssDNA-functionalized magnetic beads as a trigger chain combined with the trans-cleavage activity of the Cas12a protein and fluorescence signal amplification of the hybridization chain reaction (HCR). MCFHCR is a signal-off platform for the detection of MRSA. In the absence of DNA targets, the trans-cleavage activity of Cas12a is inactivated, allowing HCR to proceed and form long double-stranded DNA, resulting in an increased fluorescent signal. In the presence of the DNA targets, the trans-cleavage activity of CRISPR/Cas12a is activated to cleave the trigger strand, failing HCR and leading to a decrease in the fluorescence signal. Combined with RPA, MCFHCR was completed within 35 min, achieving a limit of detection (LOD) of five copies/μL for mecA DNA and 8 CFU/mL for MRSA. In detecting clinical strains, MCFHCR demonstrated comparable performance to qPCR and drug sensitivity testing. Therefore, with its simple, rapid operation and convenient signal acquisition, MCFHCR shows significant practical applicability in detecting MRSA.
研究领域:
微生物学
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分子诊断学
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CRISPR技术
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传染病检测
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生物传感器
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 15
Zhao Lu,Gu Qin,Zhou Jing,He Changting,Jia Yue,Ma Fei,Lei Hongyi,Li Bin,Liao Yuhui
Methicillin-resistant Staphylococcus aureus (MRSA)-infected burn wounds suffer from severe bacterial infection (resistant to almost all antibiotics) and intense inflammatory responses, leading to difficulty in wound healing. We designed a multifunctional cryogenic dead macrophage system (Van@AIE-CD-M) for precise, long-acting photodynamic/antibiotic MRSA eradication and broad-spectrum anti-inflammation. Cryo-dead macrophage (CD-M) carriers were prepared by freeze-killing live macrophages in liquid nitrogen, which eliminates the inflammatory side effects while preserving cellular structure and receptors. CD-M were then loaded with a high-performance aggregation-induced emission (AIE) photosensitizer TTVP on the membrane and vancomycin in the cytoplasm, yielding Van@AIE-CD-M. Following dripping onto MRSA-infected burn wounds, Van@AIE-CD-M utilized retained pattern-recognition receptors to bind MRSA, enhancing photodynamic antibacterial efficacy by bringing the bacteria close to the membrane-anchored photosensitizer. Meanwhile, pro-inflammatory cytokine receptors expressed on the Van@AIE-CD-M membrane neutralized multiple pro-inflammatory cytokines through specific receptor-ligand binding, achieving broad-spectrum anti-inflammatory effects. Moreover, Van@AIE-CD-M exhibited sustained vancomycin release, ensuring prolonged anti-infective efficacy. After treatment, Van@AIE-CD-M effectively reduced MRSA burden, pro-inflammatory cytokines, and macrophage M1 polarization, while notably increasing anti-inflammatory IL-10, macrophage M2 polarization, and angiogenesis, ultimately accelerating burn wound healing. This engineered CD-M offers a new strategy for treating burns complicated by drug-resistant bacterial infection and could be extended to other infectious diseases. Graphical
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International Journal of Nanomedicine
·
2023
·
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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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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RSC Advances
·
2024
·Vol. 14
·期 53
·39779
·
IF 3.9
Hongshuang Qin,Huaying Niu,Yanxiang Guo,Xiaoting Wang,Tao Liu,Chuanqi Zhao
Photodynamic therapy (PDT) has emerged as an effective way to deal with drug-resistant bacterial infections. Especially, blue light (BL) mediated PDT (BL-PDT) presents unique advantages in the treatments of skin infection due to the strong light absorption of superficial skin, weak penetration of BL and little damage to deep tissues. However, the photosensitizers used for BL-PDT are very limited, and the ongoing development of novel BL photosensitizers is indispensable. Porphyrins are good sources for developing efficient photosensitizers. Herein, for developing more effective BL photosensitizers, five porphyrin derivatives that can be excited by BL [5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20-tetrakis(4-bromophenyl)porphyrin (TBPP), 5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (TCPP), 5,10,15,20-tetrakis(4-fluorophenyl)porphyrin (TFPP), 5,10,15,20-tetrakis(4-iodophenyl)porphyrin (TIPP)] are subjected to the investigation of PDT against MRSA (methicillin resistant Staphylococcus aureus ). The results reveal that TBPP-mediated BL-PDT shows outstanding bactericidal effects. Mechanism studies show that TBPP + BL can induce reactive oxygen species (ROS) up-regulated in MRSA, rupture cell membrane, inhibit ATP (adenosine triphosphate) production and virulence factor expression. Furthermore, TBPP + BL effectively eliminates MRSA form biofilms, inhibits biofilm formation and disintegrates mature biofilms. More importantly, TBPP-PDT significantly accelerate mouse skin wound healing in a biofilm infection model. Our work offers new insights into the development of novel BL photosensitizers. Photodynamic therapy mediated by 5,10,15,20-tetrakis(4-bromophenyl)porphyrin (TBPP) effectively eliminates drug-resistant Staphylococcus aureus , inhibits biofilm formation and accelerates wound healing in a mouse model.
研究领域:
微生物学
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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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ACS Sensors
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2022
·
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
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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Nanoscale
·
2020
·Vol. 12
·期 14
·7651-7659
·
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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JOURNAL OF HAZARDOUS MATERIALS
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2024
·
IF 12.2
Siyuan Fu,Xuan Yi,Yi Li,Yuanhui Li,Xiaolin Qu,Peng Miao,Yuanyuan Xu
Due to the bacteria resistant to various first-line antibiotics, it is urgent to develop efficient antibiotic alternatives and formulate multidimensional strategies. Herein, supramolecular Chinese medicine nanoparticles are synthesized by self-assembly of berberine (BBR) and chlorogenic acid (CGA), which exhibit higher inhibitory effect against S taphylococcus aureus and multidrug-resistant S taphylococcus aureus (MRSA) than ampicillin, oxacillin, BBR, CGA, as well as mixture of BBR and CGA (minimum inhibitory concentration, MIC = 1.5 µM). The inhibition by BBR/CGA nanoparticles (2.5 µM) reaches 99.06 % for MRSA, which is significantly higher than ampicillin (29.03 %). The nanoparticles with 1/2 MIC can also synergistically restore the antimicrobial activity of ampicillin against MRSA. Moreover, in vivo therapeutic outcome in the murine skin wound infection model suggests that the nanoparticles are able to promote wound healing. This study provides new insights in the application of Chinese medicines self-assembly for MRSA inhibition, as well as solutions for potential persistent clinical infections and drug deficiencies.
研究领域:
药学
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纳米技术
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微生物学
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中药
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PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
·
IF 8.3
Yu Wang,Jingru Shi,Mengyao Wang,Lingjiao Zhang,Rui Wang,Junjie Zhang,Huiling Qing,Jinyou Duan,Xiaoli Zhang,Guojuan Pu
Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.
研究领域:
生物医学工程
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药学
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材料科学
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微生物学
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高影响因子
危险品化学品经营许可证（带存储）