Antimicrobial Peptide-Conjugated MoS₂-Based Nanoplatform for Multimodal Synergistic Inactivation of Superbugs

Development of new antibacterial therapeutic materials is becoming increasingly urgent due to the huge threat of superbugs, which are responsible for more than half of a million deaths each year in this world. Here, we report the development of a novel nanobiomaterial based on a melittin antimicrobial peptide (AMP)-attached transition metal dichalcogenide MoS₂-based theranostic nanoplatform. The reported nanoplatform has a capability for targeted identification and synergistic inactivation of 100% multidrug-resistant superbugs by a combined photo thermal therapy (PTT), photodynamic therapy (PDT), and AMP process. A novel approach for the design of a melittin antimicrobial peptide-attached MoS₂-based nanoplatform is reported, which emits a very bright and photo stable fluorescence. It also generates heat as well as reactive oxygen species (ROS) in the presence of 670 nm near-infrared light, which allows it to be used as a PTT and PDT agent. Due to the presence of AMP, multifunctional AMP exhibits a significantly improved antibacterial activity for superbugs via a multimodal synergistic killing mechanism. Reported data demonstrate that nanoplatforms are capable of identification of multidrug-resistant superbugs via luminescence imaging. Experimental results show that it is possible to kill only ∼45% of superbugs via a MoS₂ nanoplatform based on PTT and PDT processes together. On the other hand, killing less than 10% of superbugs is possible using melittin antimicrobial peptide alone, whereas 100% of methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Escherichia coli (E. coli), and drug-resistant Klebsiella pneumoniae (KPN) superbugs can be killed using antimicrobial peptide-attached MoS₂ QDs, via a synergistic killing mechanism. Mechanisms for possible synergistic killing of multidrug-resistant superbugs have been discussed.