A Polyoxometalate-Based Pathologically Activated Assay for Efficient Bioorthogonal Catalytic Selective Therapy.

Area of Science:

• * Materials Science
• * Nanotechnology
• * Bioorthogonal Chemistry

Background:

• * Polyoxometalates (POMs) exhibit tunable redox properties and self-assembly capabilities.
• * Copper-catalyzed azide-alkyne cycloaddition (CuAAC) faces challenges in catalytic efficiency and disease selectivity for biomedical uses.
• * Pathogen-specific triggers like acidity and hydrogen sulfide (H2S) are crucial for targeted therapies.

Purpose of the Study:

• * To develop a novel bioorthogonal catalyst for selective antibiofilm therapy.
• * To address limitations of traditional CuAAC reactions in complex biological environments.
• * To create a catalyst responsive to pathological cues for enhanced therapeutic outcomes.

Main Methods:

• * Construction of molybdenum (Mo)-based POM nanoclusters doped with copper (Cu-POM NCs).
• * Investigation of POM nanocluster responsiveness to acidic environments and H2S.
• * Evaluation of CuAAC-mediated in situ synthesis of antibacterial agents within biofilms.
• * Assessment of NIR-II photothermal effects triggered by H2S in pathogenic environments.

Main Results:

• * Cu-POM NCs demonstrated biofilm-responsive self-assembly and efficient CuAAC catalysis.
• * Selective triggering of antibacterial molecule synthesis and NIR-II photothermal effects at pathological sites.
• * Significant reduction in persister bacteria and enhanced biofilm elimination due to H2S consumption.
• * Successful demonstration of targeted antibiofilm therapy using the POM-based platform.

Conclusions:

• * Cu-POM NCs serve as an efficient and selective bioorthogonal catalyst for antibiofilm therapy.
• * The developed platform leverages POM properties for targeted drug delivery and photothermal effects.
• * This approach offers new strategies for designing advanced catalysts in disease treatment.