Frontiers in Microbiology
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2025
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IF 4.5
Yongtian Yuan,Liangliang Zhao,Zhuchun Bei,Baogang Wang,Dongna Zhang,Likun Xu,Jiahui Liu,Meng Lv,Qin Xu,Yabin Song
Introduction: Drug-resistant bacteria, particularly Acinetobacter baumannii, present a significant threat to global public health, highlighting the urgent need for novel antibacterial therapies. Drug repurposing has emerged as a promising strategy to accelerate therapeutic development by identifying new applications for existing pharmaceuticals. This study investigates the potential of naphthoquine phosphate (NQP), an antimalarial agent, as a broad-spectrum antibacterial candidate against the multidrug-resistant strain A. baumannii LAC-4.Methods: To evaluate the antibacterial activity of NQP, we determined the minimum inhibitory concentration (MIC) against Acinetobacter baumannii LAC-4. Inhibition kinetics were analyzed to assess concentration-dependent effects. Membrane permeability assays were performed to examine NQP-induced changes in cell membrane integrity. Oxidative damage tests were conducted to investigate impacts on bacterial metabolic processes. Morphological changes in A. baumannii LAC-4 treated with NQP of MIC were observed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Additionally, transcriptome analysis was performed to identify disrupted physiological pathways associated with NQP exposure.Results and discussion: NQP exhibited broad-spectrum antibacterial activity, with a MIC of 62.5 μg/mL against Acinetobacter baumannii LAC-4. Its inhibition kinetics curve confirmed a concentration-dependent inhibitory effect. Membrane permeability tests revealed that NQP disrupts cell membrane integrity, enhancing permeability—consistent with TEM/SEM observations showing significant structural damage in NQP-treated A. baumannii, including membrane rupture, cellular deformation, and cytoplasmic disorganization. Oxidative damage tests indicated NQP impacts bacterial metabolism, and transcriptome analysis further demonstrated that NQP disrupts multiple physiological pathways, primarily through enhanced membrane permeability and induced oxidative stress. These findings support NQP as a promising molecular scaffold for developing novel therapies against Acinetobacter baumannii infections, highlighting its potential in drug repurposing strategies for combating drug resistance.
研究领域:
微生物学
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药理学
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抗菌素耐药性
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细胞生物学
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分子生物学
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药物再利用
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2024
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IF 18.5
Xueqin Zhu,Xiaoxi Wang,Zimai Liu,Bing Jiang,Zonghong He,Sijia Liu,Yahong Wu,Zixian Wu,Tiantian Zhang,Meiyi Liu,Kai Li,Xiaoshuang Niu,Yanfeng Gao
Although numerous peroxidase (POD)-like nanozymes have been designed for catalytic therapy of cancer, development of nanozymes with higher therapeutic efficacy and less adverse effects are challengeable. More importantly, the underlying antitumor mechanism remains largely unknown which hinders their application. Here, the nitrogen-doped carbon nanozyme (N-PCNS) as a model is utilized and demonstrated that its capacity to specifically activate the STING pathway in tumor cells through reactive oxgen species (ROS)-mediated mitochondrial DNA (mtDNA) release, which provides the initial signals for STING-dependent innate immune response. Further, a peptide-nanozyme conjugate (PNEC, OPBP1-N-PCNS), comprising a PD-L1 blocking/targeting dual-functional peptide and a cationic-coated N-PCNS is constructed, which are conjugated through a matrix metalloproteinase responsive peptide linker. The cleaved derivate nanozyme with positive charge exhibits recyclable capacity and superior ability in capturing and enhancing the transcellular transport of tumor-derived mtDNA toward DCs, thereby amplifying the STING signaling-mediated anti-tumor immune response. This study proposed a unique mechanism and design strategy for POD-like nanozyme in cancer immunotherapy.
研究领域:
癌症免疫治疗
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纳米技术
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免疫学
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分子生物学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Jianlan Peng,Chang Liu,Meilan Mo,Yu Huang,Yeqing Lu,Mengjie Xiao,Xin Zhao,Qijun Ruan,Huihui Ti
Nanozymes have become promising alternative antibacterial agents for bacteria-infected wounds. In this study, fucoidan-confined gold nanoparticles (Fuc@AuNPs) are developed by in situ reduction, and stabilized by sulfate groups of fucoidan. Fuc@AuNPs exhibit pH-responsive catalytic activity that can mimic oxidase (OXD) under acidic bacterial infection conditions and mimic superoxide dismutase (SOD) under normal physiological conditions. The OXD-like catalytic activity of Fuc@AuNPs generates active singlet oxygen ( 1 O 2 ), exhibiting effective antibacterial properties against both Gram-negative E. coli and Gram-positive S. aureus . Fuc@AuNPs and aldehyde grafted saponin incorporate with chitosan to form a hybrid hydrogel. This hydrogel exhibits superior mechanical, adhesive, and self-healing properties due to electrostatic complex coacervation networks and dynamic covalent Schiff base reactions. Animal experiments show that the hydrogel aids S. aureus -infected skin wound healing by reducing bacterial infection and promoting granulation tissue formation without causing excessive ROS-induced inflammation. This study presents the design of multifunctional nanozymes and bioactive hydrogels as a promising wound healing dressing for biomedical applications.
研究领域:
材料科学
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纳米技术
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生物医学工程
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药学
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Fanqi Kong,Hongyue Yu,Lifei Gao,Enyun Xing,Yan Yu,Xiaofei Sun,Wenxing Wang,Dongyuan Zhao,Xiaomin Li
A persistent inflammatory response, intrinsic limitations in axonal regenerative capacity, and widespread presence of extrinsic axonal inhibitors impede the restoration of motor function after a spinal cord injury (SCI). A versatile treatment platform is urgently needed to address diverse clinical manifestations of SCI. Herein, we present a multifunctional nanoplatform with anisotropic bimodal mesopores for effective neural circuit reconstruction after SCI. The hierarchical nanoplatform features of a Janus structure consist of dual compartments of hydrophilic mesoporous silica (mSiO2) and hydrophobic periodic mesoporous organosilica (PMO), each possessing distinct pore sizes of 12 and 3 nm, respectively. Unlike traditional hierarchical mesoporous nanomaterials with dual-mesopores interlaced with each other, the two sets of mesopores in this Janus nanoplatform are spatially independent and possess completely distinct chemical properties. The Janus mesopores facilitate controllable codelivery of dual drugs with distinct properties: the hydrophilic macromolecular enoxaparin (ENO) and the hydrophobic small molecular paclitaxel (PTX). Anchoring with CeO2, the resulting mSiO2&PMO-CeO2–PTX&ENO nanoformulation not only effectively alleviates ROS-induced neuronal apoptosis but also enhances microtubule stability to promote intrinsic axonal regeneration and facilitates axonal extension by diminishing the inhibitory effect of extracellular chondroitin sulfate proteoglycans. We believe that this functional dual-mesoporous nanoplatform holds significant potential for combination therapy in treating severe multifaceted diseases.
研究领域:
神经科学
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纳米技术
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药学
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生物材料
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）