Versatile antimicrobial peptide-based ZnO quantum dots for in vivo bacteria diagnosis and treatment with high specificity

Abstract

The increased mortality caused by pathogenic bacterial infection calls for early infection diagnosis and effective antibiotic alternatives. In this work, we developed a fluorescent nano-probe named ZnO@PEP-MPA by conjugating BSA-stabilized ZnO quantum dot (ZnO@BSA) with UBI29-41, an anti-bacteria peptide fragment, and MPA, a near infrared (NIR) dye. The nanoprobe ZnO@PEP-MPA exhibited low cytotoxicity and could discriminate the bacterial infection from sterile inflammation or cancer in vivo with high specificity and low detection limitation. Based on the platform of ZnO@PEP-MPA, a theranostic nanocomposite, Van@ZnO-PEP-MPA was firstly established by further decorating ZnO@PEP-MPA with Vancomycin, a kind of glycopeptide antibiotic, which demonstrated enhanced antibacterial activity and desirable biocompatibility both in vitro and in vivo. Furthermore, another antibiotic methicillin was immobilized onto ZnO@PEP-MPA, forming Met@ZnO-PEP-MPA and demonstrated significant improved capability to combat with the anti-methicillin-resistant-bacteria in comparison with free methicillin as a result of the increased cell membrane permeation mediated by ZnO@BSA-PEP-MPA. Therefore, ZnO-PEP-MPA reported in this work holds promising potential to realize efficient non-invasive diagnosis of bacterial infections, providing important guiding information for treatment, and can be employed as drug carriers for effective bacterial-targeting therapy, favorable to hurdle multi-drug resistance after being loaded with antibiotics.

Keywords: Anti-multidrug resistance; Bacteria-targeting; Diagnosis; In vivo; Therapy; ZnO quantum dots.