EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2025
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IF 5.9
Runchu Li,Hongwei Lan,Jinyi Liu,Hui Gao,Yi Wei,Gaoteng Huang,Ying Wang,Yuxin Liu,Zihan Zhao,Li Wang,Wenjia Dan,Jiangkun Dai
The excessive and indiscriminate use of antibiotics has led to a broad increase in bacterial resistance, highlighting the critical need for the rapid development of new antibacterial agents. Herein, a collection of quaternary ammonium salts based on β -carboline skeleton was designed and prepared. Analysis of structure-activity relationships (SARs) revealed that the length of the hydrophobic chain is a critical determinant for antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Among them, compound 6d emerged as the most promising lead candidate, exhibiting strong activity against MRSA with MIC ranging from 0.25 to 0.5 μg/mL across 11 clinical isolates, while maintaining low hemolytic activity and minimal cytotoxicity toward mammalian cells. Furthermore, compound 6d displayed rapid bactericidal action at a high concentration (1 μg/mL), low propensity for inducing resistance, and good plasma stability. Notably, compound 6d demonstrated superior in vivo anti-MRSA activity and low toxicity. Further multi-target mechanistic studies indicated that compound 6d suppressed biofilm formation, compromised the cell wall, and disrupted the cytoplasmic membrane, which were accompanied by membrane depolarization, enhanced permeability, and loss of membrane integrity. Additionally, compound 6d facilitated the accumulation of reactive oxygen species (ROS), reduced metabolic activity as well as bound to DNA. Overall, these findings provide key insights for the development of quaternary ammonium salt antibacterial fusing active natural skeleton.
研究领域:
微生物学
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药物化学
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化学生物学
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抗感染药理学
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分子药理学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
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IF 8.7
Yunhao Song,Yihui Lin,Shuangshaung Li,Xueping Huang,Na Wen,Jinlin Long,Ying Wang,Pengzhao Wang,Tengfei Lin,Xunbin Yu,Shiyun Lu
Wound infections caused by bacterial invasion significantly impair tissue regeneration and prolong healing. While injectable hydrogels show promise for wound management, their clinical application is limited by pH sensitivity in infected wound microenvironments. In this study, we successfully developed a novel pH-independent antibacterial hydrogel (FHAg) via hydroxyethyl cellulose (HEC)-guided self-assembly of Fmoc-Glu-OMe and in situ synthesized silver nanoparticles (AgNPs). The HEC matrix provides a stable structural scaffold for the hydrogel, promotes π-π stacking self-assembly, and confers exceptional stability within a broad pH range (3.0–7.4), effectively overcoming the pH-sensitivity limitation of conventional hydrogels in acidic wound microenvironments. The hydrogel exhibited exceptional biocompatibility, potent antibacterial and antibiofilm activity in vitro. In vivo MRSA -infected rat wound model revealed two key advantages: 99.9% bacterial eradication efficacy and accelerated wound healing within 12 days. This pH-resilient hydrogel platform addresses critical challenges in infected wound care, showing strong potential for clinical translation.
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MATERIALS & DESIGN
·
2026
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IF 8.2
Yunxin Ye,Weian Wu,Yaping Chen,Jiyuan Zou,Ting Lin,Bo Wu,Tao Luo,Li Yang,Lvhua Guo
BCA with modified molecular skeleton exhibits potent GSH scavenging capacity. • M@PB nanozyme was designed with Pd NPs and BCA co-loaded on MPDA NPs. • M@PB achieves adaptive ROS regulation via microenvironmental pH changes. • M@PB can effectively promote the healing of MRSA-infected wounds. Nanozymes show great potential in reactive oxygen species (ROS)-based antibacterial therapy. However, bacterial glutathione (GSH)-mediated ROS scavenging and tissue damage caused by residual ROS after sterilization remain challenges. Herein, we report a ROS-adaptively regulated M@PB, which is constructed by co-loading multienzyme Pd nanoparticles and a GSH scavenger α-bromocinnamaldehyde (BCA) onto mesoporous polydopamine (MPDA). The M@PB exhibits pH-switchable enzyme-like activities: under acidic conditions, it exerts peroxidase (POD)-like activity to generate ROS for efficient bacterial elimination; as bacteria are eradicated and the local pH rebounds, it switches to catalase (CAT)-like activity to scavenge residual ROS and produce oxygen, thereby accelerating cell migration. Furthermore, backbone-modified BCA exhibits strong GSH-scavenging activity; its acid-triggered release from M@PB further disrupts bacterial antioxidant systems, driving greater oxidative stress to accelerate the antibacterial-to-healing progression. Experiments demonstrate that M@PB exhibits potent antibacterial and antioxidant properties with favorable biosafety, and can effectively promote the healing of methicillin-resistant Staphylococcus aureus ( MRSA )-infected wounds. This work provides a pH-Switchable nanoplatform that enables flexible regulation of ROS, offering a robust strategy for the care of wounds infected with drug-resistant bacteria. Download: Download high-res image (177KB) Download: Download full-size image
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CHEMICAL ENGINEERING JOURNAL
·
2026
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IF 12.5
Yonglan Yang,Qiongmei Mai,Liqiang Wang,Peiyi Huang,Yuezhao Zhou,Yujia Liu,Peiyao Wu,Fang Yang,Jie Liu,Yanan Liu
Deep pulmonary infections caused by drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are difficult to eradicate due to the combined protection of biofilms and intracellular bacterial reservoirs. Here, we report a biomimetic “Trojan Horse” nanozyme platform (HA@MSN-Cip-BM, MSM) that integrates infection-responsive drug delivery, bacterial targeting, and catalytic antibacterial activity into a single cascade-activated system. MSM is constructed by encapsulating ciprofloxacin (Cip) within aminated mesoporous silica (MSN) nanoparticles, sealing the pores with 3-aminophenylboronic-acid-modified molybdenum sulfide quantum dots (BM), and coating the surface with hyaluronic acid (HA) for cellular uptake. Upon exposure to the acidic infectious microenvironment, MSM undergoes an acid-responsive activation process characterized by enhanced ciprofloxacin release, increased accessibility of boronic-acid moieties for bacterial interaction, and ROS-associated antibacterial activity. This spatially confined activation enhances bactericidal efficacy against both biofilm-associated and intracellular MRSA. Mechanistic and transcriptomic analyses, together with evaluation in a chronic pneumonia model, demonstrate effective bacterial clearance, reduced lung inflammation, and good biocompatibility. This work establishes a cascade-responsive nanozyme design paradigm for treating drug-resistant deep lung infections.
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PROCESS BIOCHEMISTRY
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2025
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IF 4
Peili Li,Gan Zhao,Long Meng,Jumen Wei,Junhua Chen,Yunhe Xu,Da Zhang,Xiang Ke,Zirong Li
Multidrug-resistant (MDR) bacterial infections, typified by methicillin-resistant Staphylococcus aureus (MRSA), have become a severe global challenge to healthcare systems. In response, antibacterial carbon dots (CDs) have attracted growing interest in the fight against MRSA. In this study, nitrogen self-doped ginkgo leaf (GL) carbon dots (GLCDs) were synthesized through a facile one-step solvothermal method combined with extraction technology. The prepared GLCDs are spherical nanoparticles with a crystalline structure and carry a positive charge of + 7.62 mV. The minimum inhibitory concentration (MIC) of GLCDs against MRSA was found to be 250 μg/mL. Notably, at a concentration of 750 μg/mL, GLCDs could completely eliminate 1 × 10 6 MRSA within 240 minutes and effectively suppress MRSA biofilm formation in a dose-dependent manner. The antimicrobial mechanisms involve electrostatic interaction enabling penetration into MRSA, disruption of the cell structure leading to intracellular component leakage, induction of oxidative stress, and inhibition of antioxidant enzymes and respiratory function. Moreover, GLCDs demonstrated excellent biocompatibility in hemolysis and in vitro cytotoxicity tests. This research presents a novel natural-plant-based antimicrobial nanomaterial, providing valuable insights into the rational utilization of natural biomass to combat MRSA infections.
研究领域:
纳米技术
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微生物学
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材料科学
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药学
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生物医学工程
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高影响因子
Theranostics
·
2025
·Vol. 15
·期 14
·6882
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IF 13.3
Sihua Li,Junping Ma,Liuyang Zhang,Xiaoyan Qu,Long Zhang,Qian Huang,Bo Lei
Background: Wound healing impaired by multidrug-resistant bacteria (MDRB) remains a significant clinical challenge, primarily due to persistent bacterial infection, excessive inflammation, overproduction of reactive oxygen species (ROS), and compromised vascularization. Importantly, the cellular metabolic state plays a vital role in regulating cellular behavior, and strategies aimed at enhancing cellular energy metabolism hold great promise for promoting tissue regeneration. Methods: Herein, we present a multifunctional and bioactive silk fibroin-poly(citrate-curcumin)-metal-based biomimetic matrix (SFPC) designed to treat methicillin-resistant staphylococcus aureus (MRSA)-infected wounds by promoting bioenergy-induced angiogenesis. Results: SFPC exhibited robust broad-spectrum antimicrobial, anti-inflammatory, intracellular ROS-scavenging, and pro-angiogenic properties. Notably, SFPC effectively enhanced mitochondrial membrane potential and promoted adenosine triphosphate (ATP) production in HUVECs, thereby accelerating angiogenesis through the controlled release of citrate. Conclusions: This study suggests that SFPC is a promising alternative for the treatment of MRSA infected wounds and provides a facile approach for the development of a multifunctional hydrogel that promotes the healing of MRSA infected wounds at the level of cellular energy biology.
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BIOPHYSICAL CHEMISTRY
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2025
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IF 2.2
Xiaoyong Huang,Huiting Yang,Xiaomin Ren,Qianqian Li,Jianzhong Wang,Jia Cheng,Zilong Sun
Nitroxoline (NIT) is an FDA-approved antibiotic with numerous pharmacological properties. However, the intricate connections between its metal-chelating ability and antimicrobial efficacy remain incompletely understood. The specific interactions of NIT with different metal ions were measured via UV–vis absorption spectroscopy. Here, we found that NIT can bind to various metal ions, including Cu 2+ , Fe 2+ , Zn 2+ and Mn 2+ . However, the antimicrobial activity of NIT against methicillin-resistant Staphylococcus aureus (MRSA) was significantly enhanced by the inclusion of Cu 2+ as determined by a minimal inhibitory concentration (MIC) assay in Mueller-Hinton broth. The enhanced antibacterial effect was not influenced by the availability of oxygen. Mechanistically, Cu 2+ promoted bacterial proliferation, increased the bacterial transmembrane electrical potential, and increased intracellular acidification. In addition, Cu 2+ rewired bacterial metabolism, promoting the uptake of glucose with a lower level of ATP production. Pharmacological upregulation of glycolysis by VLX600 could potentiate the susceptibility of MRSA to NIT. Moreover, Cu 2+ also significantly increased the survival rate of acutely infected larvae. These collective results underscore that the enhanced antibacterial efficacy of NIT by Cu 2+ intricately involves aerobic glycolysis in MRSA.
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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PubMed
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JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-21
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IF 10.435
Xu Zhou,Deng Bin,Wang Xuewen,Yu Jie,Xu Zhuobin,Liu Penggang,Liu Caihong,Cai Yuan,Wang Fei,Zong Rongling,Chen Zhiling,Xing Hua,Chen Gang
Background Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes. Methods We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. Results The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation. Conclusion Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy. Graphical abstract
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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伤口愈合
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感染性疾病
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免疫学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Yongsheng Ni,Jingyao Wang,Mengyi Wang,Lizhi Liu,Hongqing Nie,Qiaoling Wang,Jing Sun,Tianli Yue,Ming-Qiang Zhu,Jianlong Wang
COVID-19 threatens human life because of the super destructiveness produced from its coronal morphology and strong transmembrane infection based on spike glycoprotein. Inspired by the coronal morphology of COVID-19 and its means of infecting, we designed an “artificial virus” with coronal morphology based on the concept of “defeating superbacteria with superviruses” by self-assembling a transacting activator of transduction peptide with triple-shell porous graphitic carbon nitride (g-C 3 N 4 ) embedded with cobalt nanoparticles to forcefully infect methicillin-resistant Staphylococcus aureus (MRSA). The results confirmed that this “artificial virus” had unique properties of crossing the bacterial cell membrane barrier, heating the internal bacterial microenvironment and triggering ROS outbreak, based on its coronal morphology, membrane penetration, temperature-rising and heat insulation, oxidase-like activity and excellent visible-light harvesting properties. It had a high sterilization efficiency of 99.99% at 20 min, which was 18.6 times that of g-C 3 N 4 , and the efficiency remained at 99.99% after 3 rounds of recycling and reuse. Additionally, it can rapidly inactivate bacteria in river water and accelerate wound healing.
研究领域:
生物学
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医学
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纳米医学
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抗菌研究
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Caihong Lin,Zunwei Ma,Yunpeng Gao,Mengqi Le,Zhifeng Shi,Dawei Qi,Jian-Chao Ma,Zhong-Kai Cui,Lin Wang,Yong-Guang Jia
Antibiotic-resistant bacterial infections have led to an increased demand for antibacterial agents that do not contribute to antimicrobial resistance. Antimicrobial peptides (AMPs) with the facially amphiphilic structures have demonstrated remarkable effectiveness, including the ability to suppress antibiotic resistance during bacterial treatment. Herein, inspired by the facially amphiphilic structure of AMPs, the facially amphiphilic skeletons of bile acids (BAs) are utilized as building blocks to create a main-chain cationic bile acid polymer (MCBAP) with macromolecular facial amphiphilicity via polycondensation and a subsequent quaternization. The optimal MCBAP displays an effective activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, fast killing efficacy, superior bactericidal stability in vitro, and potent anti-infectious performance in vivo using the MRSA-infected wound model. MCBAP shows the low possibility to develop drug-resistant bacteria after repeated exposure, which may ascribe to the macromolecular facial amphiphilicity promoting bacterial membrane disruption and the generation of reactive oxygen species. The easy synthesis and low cost of MCBAP, the superior antimicrobial performance, and the therapeutic potential in treating MRSA infection altogether demonstrate that BAs are a promising group of building blocks to mimic the facially amphiphilic structure of AMPs in treating MRSA infection and alleviating antibiotic resistance.
研究领域:
生物化学
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微生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF PHYSICS D-APPLIED PHYSICS
·
2024
·Vol. 57
·期 43
·435204
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IF 3.1
Pengyu Zhao,Yikang Jia,Sihong Ma,Rui Zhang,Kaiyu Li,Tianyi Song,Jianbao Zheng,Jingyao Zhang,Li Guo,Dingxin Liu,Xiaohua Wang,Mingzhe Rong
Methicillin-resistant Staphylococcus aureus (MRSA) presents a significant threat due to the multiple resistance to antibiotics, leading to severe and challenging-to-treat infections. Plasma-activated saline (PAS) prepared by plasma gases, could efficiently inactivate various pathogenic bacteria including both sensitive and antibiotic-resistant bacteria. In this study, the PAS was prepared by plasma gases with different ratios of N2 and O2 activated by gliding arc discharge. First, the gaseous reactive species in the plasma gases were compared, revealing that the highest levels of NOx including NO2 and N2O5 were generated in the gases with the N2/O2 ratios of 4:6, 5:5, and 6:4. Subsequently, the PAS prepared by the two plasma-activated gases at the N2/O2 ratios of 5:5 and 6:4 exhibited the strongest inactivation effects on both planktic MRSA and biofilms. Furthermore, the aqueous reactive species in the PAS exhibited varied change trends with the increasing N2/O2 ratios. Additionally, ultraviolet spectroscopy combined with the probe of N, N-diethyl-p-phenylenediamine was applied for the detection of O2NOO− in the PAS, and the levels of O2NOO− in the PAS were positively correlated with the inactivation effects. Moreover, the PAS induced varying levels of nitration modification on the soluble proteins in MRSA cells, which were related to the intensities of O2NOO− in the PAS. This study regulated the reactive species in the PAS through gas composition and explored the inactivation mechanism of the PAS, providing a new strategy to promote the preparation efficiency of plasma-activated solutions for biomedical applications.
研究领域:
微生物学
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生物医学工程
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感染病学
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高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2025
·
IF 6.8
Ting Xu,Zihan Xue,Xinhui Li,Miaomiao Zhang,Ruige Yang,Shangshang Qin,Yong Guo
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital- and community-acquired infections, necessitating the development of novel antibacterials. Here, we designed and synthesized 30 osthole derivatives with pyridinium quaternary ammonium moieties. In vitro bioassay showed that compounds 8u and 8ac exhibited potent antibacterial activity against S. aureus ATCC 29213 and ten clinical MRSA isolates (MIC = 0.5–1 μg/mL), with low hemolytic activity, rapid bactericidal effects, and minimal resistance induction. In MRSA-infected mouse models of skin abscesses and sepsis, 8u and 8ac also displayed excellent antibacterial effects and safety, which were comparable to vancomycin. Mechanistic studies revealed that 8u and 8ac selectively target bacterial membranes via binding to phosphatidylglycerol (PG), increasing intracellular reactive oxygen species (ROS), inducing content leakage, and ultimately causing bacterial death. These findings suggest 8u and 8ac as promising novel lead candidates for anti-MRSA drug development.
研究领域:
药理学
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微生物学
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DOI
PubMed
高影响因子
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