Photocatalytic Activation Strategy for Sequential Prodrug Release to Overcome Resistant Biofilms

Area of Science:

• Biomaterials Science
• Nanotechnology
• Antimicrobial Therapy

Background:

• Drug-resistant biofilms pose significant challenges in treating bacterial infections due to limited antibiotic penetration and increased bacterial tolerance.
• Sequential release of therapeutic agents is crucial for biofilm dispersion and subsequent bacterial eradication, but achieving this in a single system is difficult.

Purpose of the Study:

• To develop a single-component nanoconfined photocatalytic platform for the sequential release of nitric oxide (NO) and levofloxacin (LEV).
• To synchronize NO-mediated biofilm dispersion and sensitization with LEV-mediated bacterial killing for enhanced antibiofilm efficacy.

Main Methods:

• Fabrication of a single-component prodrug system utilizing a nanoconfined photocatalytic platform.
• Demonstration of sequential release of NO followed by LEV upon photocatalytic activation.
• In vivo evaluation of the platform's efficacy in a diabetic mouse model infected with levofloxacin-resistant *Pseudomonas aeruginosa*.

Main Results:

• The platform successfully achieved temporally resolved, sequential release of NO and LEV from a single component.
• Nitric oxide (NO) downregulated antibiotic-resistant gene expression and enhanced bacterial susceptibility to levofloxacin (LEV).
• The synchronized sequential therapy eradicated biofilms, accelerated wound closure, and reduced inflammation in infected diabetic mice.

Conclusions:

• The developed nanoconfined photocatalytic platform enables precise, sequential drug delivery from a single component, overcoming challenges in treating resistant biofilms.
• This strategy offers a potent approach for combating levofloxacin-resistant *Pseudomonas aeruginosa* infections.
• The one-component sequential release paradigm holds broad translational potential for various therapeutic applications beyond antibiofilm treatments.