Thiol-Binding Nanoparticles for Eradicating Bacterial Persister Cells
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Solution Overview
Problem
Current antibiotic treatments are ineffective against recalcitrant bacterial infections due to the presence of persister cells, which are dormant and highly tolerant of traditional antibiotics, especially in biofilms, leading to prolonged hospital stays and significant economic impact.
Innovation Solution
Development of nanoparticles with a thiol-binding metallic core conjugated to fluoroquinolone antibiotics, such as ciprofloxacin, which are biocompatible and capable of targeting and eradicating persister cells in both planktonic and biofilm bacteria by enhancing antibiotic efficacy through increased ROS production and cellular penetration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional antibiotics are used to treat bacterial infections, then active bacterial cells can be killed, but dormant persister cells in biofilms remain tolerant and resistant
Solution Approach 1:
The patent changes the physical and chemical parameters of the antibiotic delivery system by using nanoparticles with metallic cores (gold, silver, iron oxide) conjugated to fluoroquinolone antibiotics. This nanoparticle formulation alters drug release kinetics, cellular uptake mechanisms, and intracellular distribution, enabling the antibiotic to effectively reach and kill dormant persister cells that are tolerant to conventional antibiotic administration
Solution Approach 2:
The invention creates a composite material consisting of a metallic nanoparticle core conjugated to fluoroquinolone antibiotic molecules. This composite structure combines the advantages of metallic nanoparticles (enhanced cellular penetration, controlled release, imaging capabilities) with the antibiotic's bactericidal activity, resulting in a system that can penetrate biofilms and eradicate both active and dormant bacterial cells
2Reliability
If bacteria form biofilms, then protective habitat is provided for persisters and VBNC, but treatment complexity and duration increase
Solution Approach 1:
The patent segments the antibiotic delivery system into nanoparticle-sized units that can individually penetrate through the biofilm matrix and reach persister cells embedded within the protective biofilm structure. This segmentation allows the antibiotic to bypass the biofilm's protective barriers and directly contact dormant bacteria, enabling effective treatment without prolonged hospital stays
3Reliability
If antibiotic adjuvants are used to enhance drug activity, then resistance can be minimized, but additional compounds and mechanisms are required
Solution Approach 1:
The patent merges the antibiotic and adjuvant functions into a single integrated nanoparticle system. The metallic core provides adjuvant effects (enhanced penetration, ROS generation, immunomodulation) while the conjugated fluoroquinolone delivers bactericidal activity, eliminating the need for separate adjuvant compounds and simplifying the treatment mechanism
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The nanoparticles effectively eradicate persister cells and biofilm bacteria, including multidrug-tolerant strains, by increasing the susceptibility of persister cells to fluoroquinolone antibiotics, thereby addressing the challenge of antibiotic resistance and improving treatment outcomes for chronic infections.
Implementation Method 1
nanoparticles comprising a thiol-binding metallic core conjugated to a fluoroquinolone antibiotic
Implementation Method 2
enhancing antibiotic efficacy through increased ROS production
Data Source
AI summary
Compositions, methods, and kits are provided for treating bacterial infections with nanoparticles comprising a thiol-binding metallic core conjugated to a fluoroquinolone antibiotic. Recalcitrant infections are often difficult to treat because of the presence of persister cells, a subpopulation of bacterial cells that is highly tolerant of traditional antibiotics. Persister cells are dormant, which makes them less susceptible to many antibiotics, which are designed to kill growing cells. Administration of nanoparticles comprising a thiol-binding metallic core conjugated to fluoroquinolone antibiotics was found to be highly efficacious in eradicating persister cells and for treating infections for a broad range of bacterial species, including Gram-positive and Gram-negative bacteria. Such treatment was effective not only in eradicating planktonic bacteria but also bacteria in biofilms.