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 MnO_(2)nanosheets(MnO_(2)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,MnO_(2)NSs were modified with bovine serum albumin(BSA)and polyethylene glycol(PEG)and then loaded with chlorin e_(6)(Ce_(6))as photosensitizer to form MnO_(2)-BSA/PEG-Ce_(6)nanosheets(MBP-Ce_(6)NSs).After being delivered into the bacterial biofilm-infected tissues,the MBP-Ce_(6)NSs could be decomposed in acidic biofilm microenvironment and release Ce_(6)with Mn^(2+),which subsequently activate both fluorescence(FL)and magnetic resonance(MR)signals for effective dual-mode FL/MR imaging of bacterial biofilm infections.Meanwhile,MnO_(2)could catalyze the decomposing of H2O_(2)in biofilm-infected tissues into O_(2)and relieve the hypoxic condition of biofilm,which significantly enhances the efficacy of aPDT.An in vitro study showed that MBP-Ce_(6)NSs could significantly reduce the number of methicillin-resistant Staphylococcus aureus(MRSA)in biofilms after 635nm laser irradiation.Guided by FL/MR imaging,MRSA biofilm-infected mice can be efficiently treated by MBP-Ce_(6)NSs-based aPDT.Overall,MBP-Ce_(6)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.