pH-Responsive Micelles as Theranostic Agents for Sonodynamic Therapy and MR Imaging of Liver Abscesses

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Infectious Diseases

Background:

• Pyogenic liver abscesses (PLA) caused by Klebsiella pneumoniae (K. pneumoniae) present treatment challenges due to biofilm formation and reduced antibiotic efficacy.
• The infection microenvironment in PLA can hinder conventional therapeutic approaches.

Purpose of the Study:

• To develop a pH-responsive micelle system for targeted delivery of levofloxacin (antibiotic) and manganese porphyrin (sonosensitizer).
• To enable imaging-guided, microenvironment-triggered sonodynamic-antibiotic therapy for K. pneumoniae-associated liver abscesses (KLA).

Main Methods:

• Co-loading levofloxacin and manganese porphyrin into pH-responsive PC7A micelles.
• Utilizing ultrasound (US) for sonodynamic therapy (SDT) and MRI for lesion localization and monitoring.
• Evaluating the system's efficacy in vitro against K. pneumoniae biofilms and in vivo using a murine KLA model.

Main Results:

• Micelles selectively disassemble in acidic infection niches, releasing therapeutic payloads.
• MnTPP generates reactive oxygen species upon US exposure, disrupting biofilms and enhancing antibiotic action.
• In vivo studies demonstrated reduced bacterial burden, decreased inflammation, and promoted hepatic repair in MRI-guided treated mice.

Conclusions:

• The developed theranostic system integrates microenvironment sensing, controlled release, SDT, and MRI navigation.
• This approach offers a promising precision strategy for managing deep-seated, drug-resistant K. pneumoniae infections and KLA.
• The system effectively inhibits biofilm formation and eradicates LEV-resistant K. pneumoniae, suppressing resistance emergence.