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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Multi-comparted microgels delivering human derived probiotics and deferoxamine for multidrug-resistant infection and healing

Chao Hua,Fengbo Yang,Xiaoli Jia,Yichi Lu,Xiaoxiao Li,Peng Zhao,Malcolm Xing,Guozhong Lyu

Infection and vascular dysfunction are two major reasons for delayed wound healing, especially in the scenario of multidrug-resistant bacterial has been a challenge for antibiotics usage. Probiotics are effective in fighting pathogens, while avoiding the destruction of skin microbiome. However, the viability of probiotics is a major obstacle in clinical application. As a non-protein proangiogenic drug, deferoxamine (DFO) has significant advantages over traditional growth factors in terms of cost, storage and transportation conditions, and stability. However, there is still a problem of short half-life that requires reliable drug delivery carriers to maximize its effect. Here, we developed multiple-chambered microgels using electrospray and microfluidics. Lactobacillus fermentum (LF) and DFO, respectively, for the management of multidrug-resistant Pseudomonas aeruginosa (MPA) and promotion of wound healing. We first tested five probiotics isolated from healthy people and found LF inhibiting the growth of MPA by lowering local pH and antimicrobial substances. The multi-chambered microgels effectively inhibited MPA by delivering probiotics, they can also protect probiotics from antibiotics. DFO promoted the angiogenesis of human umbilical venous endothelial cells. The microgel system had good biocompatibility and hemocompatibility. In a MPA infected wound, the microgel system effectively alleviated wound infection by 87.44%, improved angiogenesis by 29.32% and accelerated wound healing. This work suggests that multi-compartmented microgels loaded with probiotics and deferoxamine have great potential in wounds with multidrug-resistant bacteria.

CAS / MDL: 10043-52-4 9005-38-3
研究领域: 生物医学工程 · 微生物学 · 药剂学
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Theranostics · 2019 · IF 8.063

Effective targeted therapy for drug-resistant infection by ICAM-1 antibody-conjugated TPGS modified β-Ga2O3:Cr3+ nanoparticles

Xu-Qi Kang,Gao-Feng Shu,Sai-Ping Jiang,Xiao-Lin Xu,Jing Qi,Fei-Yang Jin,Di Liu,Yong-Hong Xiao,Xiao-Yang Lu,Yong-Zhong Du

The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared β-Ga 2 O 3 :Cr 3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga 2 O 3 ) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods : I-TPGS/Ga 2 O 3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga 2 O 3 /TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga 2 O 3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga 2 O 3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga 2 O 3 /TIG were finally evaluated using acute pneumonia mice. Results : It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga 2 O 3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo . Additionally, targeted delivery of I-TPGS/Ga 2 O 3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion : It is of great value to apply I-TPGS/Ga 2 O 3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.

研究领域: 药学 · 生物医学工程 · 微生物学
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Advanced Healthcare Materials · 2024 · IF 10

NIR-Actuated Botanicals/Nanozymes Nanofibrous Membranes for Antibiotic-Free Triple-Synergistic Therapy Against Polymicrobial Wound Infections

Kai Dong,Wenbo Lin,Tianyu Zhu,Shuwen Sun,Chenhao Zhang,Chen Xu,Fangfang Cao,Xiaoyuan Chen

Polymicrobial wound infection represents a significant contributor to infectious disease-related morbidity and mortality globally. Traditionally, the management of such infection relies heavily on high doses of antibiotics, often resulting in systemic side effects and exacerbating antibiotic resistance. Consequently, there is an urgent need to develop a safe and effective platform for antibiotic-free treatment of polymicrobial wound infections. In this study, a near-infrared (NIR) light-actuated nanofibrous membrane incorporating botanicals and nanozymes is presented for antibiotic-free triple-synergistic therapy against polymicrobial wound infections. The membrane integrates berberine hydrochloride (BBH)-loaded hollow zinc-doped carbon nanocubes into polyvinyl alcohol (PVA) nanofibrous membranes. Upon low-intensity 808 nm NIR laser irradiation (0.3 W cm −2 ), the membrane achieved a controlled release of BBH and enhanced peroxidase-like (POD-like) enzyme activity. This NIR light-actuated botanical/photothermal therapy (PTT)/chemodynamic therapy (CDT) system demonstrated high efficacy in eradicating methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa both in vitro and in vivo. Furthermore, it mitigated inflammation and promoted wound healing in polymicrobial infection wounds, highlighting its potential as a promising alternative to antibiotic-based therapies.

研究领域: 生物医学工程 · 材料科学 · 微生物学
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APPLIED AND ENVIRONMENTAL MICROBIOLOGY · 2024 · IF 3.9

Novel inhibition of Staphylococcus aureus sortase A by plantamajoside: implications for controlling multidrug-resistant infections

Yujia Chen,Wei Li,Li Wang,Bingmei Wang,Jian Suo

In confronting the significant challenge posed by multidrug-resistant (MDR) pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), the development of innovative anti-infective strategies is essential. Our research focuses on sortase A (SrtA), a vital enzyme for anchoring surface proteins in S. aureus. We discovered that plantamajoside (PMS), a phenylpropanoid glycoside extracted from Plantago asiatica L. (Plantaginaceae), acts as an effective and reversible inhibitor of SrtA, with a notable IC50 value of 22.93 µg/mL. This breakthrough provides a novel approach to combat both resistance and virulence in MRSA. PMS significantly inhibits S. aureus adhesion to fibrinogen, reducing biofilm formation and hindering the anchoring of staphylococcal protein A to the cell wall. Live-dead cell assays demonstrated increased survival rates in PMS-treated MRSA-infected A549 cells. Fluorescence quenching experiments revealed a robust interaction between PMS and SrtA, with mechanistic analyses pinpointing the critical R197 amino acid residue as the target site. In vivo, PMS was highly effective in a Galleria mellonella infection model, reducing mortality rates in MRSA-infected larvae. Additionally, PMS demonstrated therapeutic efficacy in a mouse pneumonia model, improved survival rates, reduced the bacterial load in pulmonary tissues, and mitigated lung damage. These results validate PMS as a promising compound to mitigate MRSA virulence and thwart resistance by targeting SrtA. This study highlights PMS as a leading candidate for controlling MRSA infections, showing the potential of targeting specific bacterial mechanisms in the fight against MDR infections.

研究领域: 微生物学 · 药理学 · 传染病学 · 分子生物学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Smart eutectogel with antibacterial activity for efficiently treating multidrug resistant infection, real-time monitoring and diabetic wound repair

Zijie Wang,Baiwen Qi,Ruizi Wang,Ze Chen,Jingming Zhong,Zheng Wang,Qingfeng Sun,Aixi Yu,Xiaoping Shen,Hongxia Xie

Intelligent gel dressings that integrate therapeutic functions with real-time monitoring capabilities have shown considerable promise in diabetic wound treatment. However, current smart dressings often ignore issues such as resistant bacteria infections and the long-term monitoring stability. Herein, a smart cellulose-based eutectogel dressing with high sensitivity, long-term stability, and excellent anti-drug resistant bacteria activities is devised using deep eutectic solvent (DES)-replacement method for the promotion of infected diabetic wound repair and real-time monitoring of wound status. Benefiting from multiple hydrogen bonding, chemical cross-linking and electrostatic interactions, the obtained eutectogels exhibit excellent mechanical properties (16.83 kPa stress and 190.32 % strain), good conductivity (1.14 S/m), and environmental tolerance. Furthermore, the eutectogels demonstrate outstanding temperature-responsive properties (TCR = −0.99 %/°C), which could accurately and steadily sense wound temperature fluctuations for real-time monitoring of the healing status. Additionally, the biocompatible eutectogels efficiently eliminate multidrug-resistant bacteria (reached 99.99 %), attributed to disruption of bacterial membrane through electrostatic interaction. Notably, in vitro biofilm studies confirmed the eutectogels effectively prevent multidrug-resistant bacteria biofilm formation. The in vivo experiments on Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds have demonstrated that the eutectogels can effectively inhibit bacteria growth, reduce inflammatory response, promote collagen deposition and accelerate diabetic wounds healing. This work presents a promising therapeutic approach for the diagnosis and therapy in MRSA-infected chronic diabetic wounds.

研究领域: 生物材料 · 生物医学工程 · 伤口愈合 · 抗菌治疗 · 智能传感器 · 纳米技术 · 组织工程 · 传染病学 · 糖尿病研究
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