Biofilm Microenvironment-Responsive Nanotheranostics for Dual-Mode Imaging and Hypoxia-Relief-Enhanced Photodynamic Therapy of Bacterial Infections

The formation of bacterial biofilms closely associates with infectious diseases. Until now, precise diagnosis and effective treatment of bacterial biofilm infections are still in great need. Herein, a novel multifunctional theranostic nanoplatform based on MnO2 nanosheets (MnO2 NSs) has been designed to achieve pH-responsive dual-mode imaging and hypoxia-relief-enhanced antimicrobial photodynamic therapy (aPDT) of bacterial biofilm infections. In this study, MnO2 NSs were modified with bovine serum albumin (BSA) and polyethylene glycol (PEG) and then loaded with chlorin e6 (Ce6) as photosensitizer to form MnO2-BSA/PEG-Ce6 nanosheets (MBP-Ce6 NSs). After being delivered into the bacterial biofilm-infected tissues, the MBP-Ce6 NSs could be decomposed in acidic biofilm microenvironment and release Ce6 with Mn2+, which subsequently activate both fluorescence (FL) and magnetic resonance (MR) signals for effective dual-mode FL/MR imaging of bacterial biofilm infections. Meanwhile, MnO2 could catalyze the decomposing of H2O2 in biofilm-infected tissues into O2 and relieve the hypoxic condition of biofilm, which significantly enhances the efficacy of aPDT. An in vitro study showed that MBP-Ce6 NSs could significantly reduce the number of methicillin-resistant Staphylococcus aureus (MRSA) in biofilms after 635 nm laser irradiation. Guided by FL/MR imaging, MRSA biofilm-infected mice can be efficiently treated by MBP-Ce6 NSs-based aPDT. Overall, MBP-Ce6 NSs not only possess biofilm microenvironment-responsive dual-mode FL/MR imaging ability but also have significantly enhanced aPDT efficacy by relieving the hypoxia habitat of biofilm, which provides a promising theranostic nanoplatform for bacterial biofilm infections.