Bacteria-Responsive Nanoliposomes as Smart Sonotheranostics for Multidrug Resistant Bacterial Infections

Rapid emergence of multidrug resistant (MDR) "superbugs" poses a severe threat to global health. Notably, undeveloped diagnosis and concomitant treatment failure remain highly challenging. Herein, we report a sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT). Using maltohexaose-decorated cholesterol and bacteria-responsive lipid compositions, a smart nanoliposomes platform (MLP18) was developed for precise delivery of purpurin 18, a potent sonosensitizer proved in this study. Taking advantage of the bacteria-specific maltodextrin transport pathway, the prepared MLP18 can specifically target the bacterial infection site and accurately distinguish the foci from sterile inflammation or cancer with a highly selective fluorescence/photoacoustic signal on the bacteria-infected site of mice. Moreover, the bacteria-responsive feature of MLP18 activated an efficient release and internalization of high concentration sonosensitizer into bacterial cells, resulting in effective sonodynamic elimination of MDR bacteria. In situ MRI monitoring visualized such potent sonodynamic activity and indicated that MLP18-mediated SDT could successfully eradicate inflammation and abscess from mice with bacterial myositis. In view of the above advantages, the developed nanoliposomes may serve as a promising sonotheranostic platform against MDR bacteria in the areas of healthcare.