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Updated: Oct 11, 2025
Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes
Published on: March 2, 2020
Traceless antibiotic-crosslinked micelles for rapid clearance of intracellular bacteria
Xingyue Yang1, Qian Qiu1, Gengqi Liu1
1School of Chemical Engineering and Technology, Tianjin University, 300350, PR China; Key Laboratory of Systems Bioengineering (Ministry of Education) Tianjin University, Tianjin 300072, PR China.
Abstract:
Effective delivery of antimicrobial agents to intracellular pathogens represents a major bottleneck for a wide variety of infectious diseases. To address this, we developed SIR-micelles(+), as a new delivery vehicle comprising antibiotic-loaded micelles with rapid self-immolation within cells for targeted delivery to macrophages, where most intracellular bacterial reside. After phagocytosis, SIR-micelles(+) rapidly release the pristine antibiotic after the cleavage of the disulfide bonds by intracellular reducing agents such as glutathione (GSH). Colistin, a hydrophilic and potent "last-resort" antibiotic used for the treatment of drug-resistant bacterial infection, was encapsulated in SIR-micelles with 40% yield and good short-term storage stability. Hydrophobic moieties and mannose ligands in SIR-micelles(+) enhanced the delivery of colistin into macrophages. The traceless and thiol-responsive release of colistin effectively eliminated intracellular Escherichia coli within twenty minutes. In a murine pneumonia model, SIR-micelles(+) significantly reduced bacterial lung burden of multidrug-resistant Klebsiella pneumoniae. Furthermore, SIR-micelles(+) improved the survival rate and reduced the bacterial burden of organs infected by intracellular bacteria transferred from donor mice. Using this formulation approach, the nephrotoxicity and neurotoxicity induced by antibiotic were reduced by about 5- 15 fold. Thus, SIR-micelles(+) represent a new class of material that can be used for targeting treatment of intracellular and drug-resistant pathogens.
Insights
Researchers developed SIR-micelles(+), a novel drug delivery system for targeting intracellular bacterial infections. This system effectively delivers antibiotics to macrophages, reducing bacterial load and toxicity in preclinical models.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Infectious Diseases
Background:
- Effective delivery of antimicrobials to intracellular pathogens is a significant challenge in treating infectious diseases.
- Macrophages are key reservoirs for many intracellular bacteria.
Purpose of the Study:
- To develop and evaluate SIR-micelles(+), a novel self-immolating micelle system for targeted intracellular drug delivery.
- To assess the efficacy of SIR-micelles(+) loaded with colistin against intracellular bacterial infections.
Main Methods:
- Development of antibiotic-loaded micelles with disulfide bonds for intracellular release.
- Encapsulation of colistin within SIR-micelles(+).
- In vitro and in vivo evaluation in macrophage models and murine pneumonia models.
Main Results:
- SIR-micelles(+) demonstrated efficient colistin delivery into macrophages.
- Rapid, traceless release of pristine colistin triggered by intracellular glutathione.
- Significant reduction of intracellular Escherichia coli and multidrug-resistant Klebsiella pneumoniae in vivo.
- Reduced antibiotic-induced nephrotoxicity and neurotoxicity by 5-15 fold.
Conclusions:
- SIR-micelles(+) represent a promising new platform for targeted treatment of intracellular and drug-resistant bacterial pathogens.
- This formulation enhances antibiotic efficacy while mitigating systemic toxicity.
