Neutrophil-mediated delivery of the combination of colistin and azithromycin for the treatment of bacterial infection

Gao, Jiacong; Hu, Xueyan; Xu, Congjuan; Guo, Mingming; Li, Shouyi; Yang, Fan; Pan, Xiaolei; Zhou, Fangyu; Jin, Yongxin; Bai, Fang; Cheng, Zhihui; Wu, Zhenzhou; Chen, Shuiping; Wu, Weihui

doi:10.1016/j.isci.2022.105035

Cited by 5 publications

(3 citation statements)

References 83 publications

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“…Furthermore, macrolides have been shown to decrease the expression of adhesion molecules, which may contribute to reducing airway neutrophilic infiltration 24,25 . Most recently, Gao and colleagues recently established that AZM‐loaded neutrophils demonstrated enhanced bactericidal abilities against PA, reduced inflammatory cytokines production, and protected mice from PA acute pneumonia 26 . Therefore, changes in neutrophils' behaviors when exposed to AZM could explain the reduction of their influx in the lungs.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Most recently, Gao and colleagues recently established that AZM-loaded neutrophils demonstrated enhanced bactericidal abilities against PA, reduced inflammatory cytokines production, and protected mice from PA acute pneumonia. 26 Therefore, changes in neutrophils' behaviors when exposed to AZM could explain the reduction of their influx in the lungs. On the other hand, recent evidence of emerging resistance due to ribosomal protein mutations under AZM therapy supports direct anti-PA activity of AZM.…”

Section: Discussionmentioning

confidence: 99%

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Azithromycin regulates bacterial virulence and immune response in a murine model of ceftazidime‐treated Pseudomonas aeruginosa acute pneumonia

Leroy,

Caillon,

Broquet

et al. 2023

Microbiology and Immunology

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Pseudomonas aeruginosa (PA) remains one of the leading causes of nosocomial acute pneumonia. The array of virulence factors expressed by PA and the intense immune response associated with PA pneumonia play a major role in the severity of these infections. New therapeutic approaches are needed to overcome the high resistance of PA to antibiotics and to reduce the direct damage to host tissues. Through its immunomodulatory and anti‐virulence effects, azithromycin (AZM) has demonstrated clinical benefits in patients with chronic PA respiratory infections. However, there is relatively little evidence in PA acute pneumonia. We investigated the effects of AZM, as an adjunctive therapy combined with ceftazidime (CAZ), in a murine model of PA acute pneumonia. We observed that the combined therapy (i) reduces the weight loss of mice 24 h post‐infection (hpi), (ii) decreases neutrophil influx into the lungs at 6 and 24 hpi, while this effect is absent in a LPS‐induced pneumonia or when PA is pretreated with antibiotics and mice do not receive any antibiotics, and that (iii) AZM, alone or with CAZ, modulates the expression of PA quorum sensing regulators and virulence factors (LasI, LasA, PqsE, PhzM, ExoS). Our findings support beneficial effects of AZM with CAZ on PA acute pneumonia by both bacterial virulence and immune response modulations. Further investigations are needed to clarify the exact underlying mechanisms responsible for the reduction of the neutrophils influx and to better discriminate between direct immunomodulatory properties of AZM, and indirect effects on neutrophilia resulting from bacterial virulence modulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Azithromycin regulates bacterial virulence and immune response in a murine model of ceftazidime‐treated Pseudomonas aeruginosa acute pneumonia

Leroy,

Caillon,

Broquet

et al. 2023

Microbiology and Immunology

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“…In addition, Ju et al believe that neutrophil‐based drug delivery systems retain their function after the delivery of NP drug particles. For example, in mice with acute pneumonia, neutrophils carrying colistin and azithromycin NPs can still produce ROS, which effectually protects the mice from bacterial infection (Gao et al, 2022).…”

Section: Mechanism Of Action Of Drugs Mediated By Neutrophil Hitchhikingmentioning

confidence: 99%

Neutrophil hitchhiking: Riding the drug delivery wave to treat diseases

Wang,

Jin,

Huang

et al. 2024

Drug Development Research

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Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease treatment. This article provides an overview of the innovative and feasible application of neutrophils as drug carriers. It explores the mechanisms underlying neutrophil function, elucidates the mechanism of drug delivery mediated by neutrophil‐hitchhiking, and discusses the potential applications of this strategy in the treatment of cancer, immune diseases, inflammatory diseases, and other medical conditions.

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Recent Progress in Therapeutic Strategies and Biomimetic Nanomedicines Based on Neutrophils for Inflammation Treatment

Liu

Wang

et al. 2023

Nanomedicine (Lond.)

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Inflammation is a defensive response that helps repair and restore damaged tissue by activating immune and nonimmune cells against pathogens. However, inflammation may cause chronic disease if it persists for a long time. Neutrophils recruit immediately to the lesion site and regulate the inflammatory process when inflammation occurs. Therefore, neutrophil-mediated therapy has been considered as a promising strategy for inflammatory diseases and has been extensively studied. In this review, we summarize the recent research progress of neutrophil-based personalized treatment strategies for inflammation. We also review the research progress of various neutrophil-mediated drug-delivery systems in combination with the inflammatory microenvironment.

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Neutrophil-mediated delivery of the combination of colistin and azithromycin for the treatment of bacterial infection

Cited by 5 publications

References 83 publications

Azithromycin regulates bacterial virulence and immune response in a murine model of ceftazidime‐treated Pseudomonas aeruginosa acute pneumonia

Azithromycin regulates bacterial virulence and immune response in a murine model of ceftazidime‐treated Pseudomonas aeruginosa acute pneumonia

Neutrophil hitchhiking: Riding the drug delivery wave to treat diseases

Recent Progress in Therapeutic Strategies and Biomimetic Nanomedicines Based on Neutrophils for Inflammation Treatment

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