pH-Responsive Micelles as Theranostic Agents for Sonodynamic Therapy and MR Imaging of Liver Abscesses
Abstract
Pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae(K. pneumoniae) remains challenging to treat due to the lesion microenvironment that fosters biofilm formation and compromises antibiotic efficacy. Herein, we develop pH-responsive PC7A micelles co-loaded with levofloxacin (LEV) and manganese porphyrin (MnTPP) for imaging-guided, microenvironment-triggered sonodynamic-antibiotic therapy. The micelles remain stable under physiological conditions but selectively disassemble in mildly acidic infection niches, enabling the on-demand release of therapeutic payloads. Upon ultrasound (US) exposure, MnTPP acts as an efficient sonosensitizer to generate reactive oxygen species for biofilm disruption, while its paramagnetic property concurrently enhances T1-weighted MRI for real-time lesion localization and longitudinal treatment monitoring. In vitro, this platform effectively inhibits biofilm formation and eradicates LEV-resistant K. pneumoniae while also suppressing the emergence of drug-resistant variants compared to monotherapy. In vivo, MRI-guided treatment in a murine Klebsiella pneumoniae-associated liver abscess (K. pneumoniae liver abscess, KLA) model significantly reduces intra-abscess bacterial burden and inflammatory markers while promoting hepatic tissue repair. By integrating microenvironment sensing, controlled release, SDT potentiation, and MRI navigation, this theranostic system addresses key challenges in managing deep-seated, drug-resistant infections and…
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