Precise magnetic resonance imaging-guided sonodynamic therapy for drug-resistant bacterial deep infection

The precise treatment of drug-resistant deep bacterial infections remains a huge challenge in clinic. Herein, a polymer-peptide-porphyrin conjugate (PPPC), which can be real-time monitored in infectious site, is developed for accurate and deep sonodynamic therapy (SDT) based on in vivo self-assembly strategy. The PPPC contains four moieties, i.e., a hyperbranched polymer backbone, a self-assembled peptide linked with an enzymecleavable peptide-poly (ethylene glycol) terminal, a bacterial targeting peptide, and a porphyrin sonosensitizer (MnTCPP) segment. Once PPPC nanoparticles reach the infectious area, the protecting PEG layers are removed due to the over-expressed gelatinase, leading to the secondary assembly into large nanoaggregates and resultant enhanced accumulation of sonosensitizer. The nanoaggregates exhibit enhanced interaction with bacterial membrane and decrease the minimum inhibitory concentration (MIC) significantly. Meanwhile, compared with free MnTCPP, the concentration of which can not be accurately quantified, the accumulation amount of MnTCPP in PPPCs at infectious site can be in situ monitored by magnetic resonance imaging (MRI) using T-1 combined with T-2. When the concentration of PPPC-1 reaches MIC, the drug-resistant bacterial infection area is exposed to ultrasound irradiation, causing the precise and efficient elimination of bacteria. Therefore, the MRI-guided SDT system shows extraordinary tissue penetration depth, drug concentration monitoring, morphology-transformation induced accumulation and improved treatment capacity toward drug-resistant bacteria.

Automated summary

The study introduces a novel approach for treating drug-resistant deep bacterial infections using a polymer-peptide-porphyrin conjugate (PPPC) to achieve accurate and deep sonodynamic therapy (SDT). PPPC can be monitored in real-time at the infectious site and effectively eliminates drug-resistant bacteria, showing promising applications in the field.