Abstract
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.
Highlights
Bacterial infection is a prominent threat for human health
Manganese (II) chloride reacted with H2O2 and tetramethylammonium hydroxide (TMA·OH) to form aggregated MnO2 NSs (Figure S1, Supporting Information)
Masson’s trichrome staining images further indicate the formation of intact subcutaneous tissues and the appearance of more collagen fibers in group 5 than the other groups, suggesting better recovery of the infected tissues. These results demonstrated that MBPCe6 NSs have excellent antimicrobial photodynamic therapy (aPDT) efficacy for methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections, which should be ascribed to the hypoxia-relief in the biofilm microenvironment
Summary
Bacterial infection is a prominent threat for human health. Numerous bacterial infections, including dental caries, cystic fibrosis, pneumonia, otitis media, and especially chronic wounds, usually relate with the formation of bacterial biofilms [1,2,3,4,5]. The compact EPS of bacterial biofilm protect themselves from the attack of host immune system and cause serious antibiotic resistance, which bring great challenge to eradicate bacterial biofilm infections [8, 9]. Specific and sensitive diagnosis of bacterial biofilm infections is essential to effectively treat these diseases [10,11,12]. Traditional diagnostic methods, such as culture method, biochemistry identification, and polymerase chain reaction (PCR), have been widely used in bacterial biofilm infections diagnosis.these ex vivo methods generally need invasive tissue ablation, time-consuming procedures, Research
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