Acid-Triggered, Enzyme-Enabled EPS-Degrading Nanoplatform With Enhanced In Situ Retention for Intravenous Biofilm...

Area of Science:

• Biomaterials Science
• Nanomedicine
• Infectious Disease Therapy

Background:

• Bacterial biofilms pose significant challenges to conventional antibacterial treatments due to their protective extracellular polymeric substance (EPS) matrix.
• Limited nanoparticle penetration and reduced drug efficacy are key issues in treating biofilm-associated infections.

Purpose of the Study:

• To develop a multifunctional nanosystem for efficient in vivo treatment of biofilm-associated infections.
• To create a pH-responsive, surface charge-adaptive system integrating multiple therapeutic and diagnostic modalities.

Main Methods:

• Self-assembly of liposomes encapsulating bromelain and an NIR-II photothermal agent (DTTB).
• Surface modification with DA-functionalized chitosan (CS-DA) for charge adaptation and prolonged circulation.
• Utilizing pH-triggered charge restoration, in situ self-aggregation, photothermal hyperthermia, enzymatic EPS degradation, and NIR-II imaging.

Main Results:

• The nanosystem demonstrated 99.99% eradication efficiency against methicillin-resistant Staphylococcus aureus biofilms in vitro.
• Achieved enhanced biofilm penetration and retention at infection sites in vivo.
• Enabled high-contrast NIR-II imaging, accelerated wound healing, and showed therapeutic efficacy in deep pulmonary infections.

Conclusions:

• The developed nanosystem offers a versatile intravenous strategy for targeted, synergistic therapy against biofilm-associated infections.
• The pH-responsive, charge-adaptive approach shows significant potential for overcoming challenges in biofilm treatment.
• This multifunctional platform integrates imaging and therapy for comprehensive management of complex infections.