Addressing Multidrug-resistant Bacterial Infections with Iridium-based Theragnostic Agents

Abstract

Effective strategies are essential for addressing bacterial infections caused by antimicrobial resistance (AMR). The increasing interest in transition-metal complexes stems from their fluorescence properties and diverse mechanisms of action against bacteria, making them promising single-molecule theragnostic agents. In this study, we report the development of an amphiphilic cyclometalated iridium complex (Ir-NH2) that forms positively charged spherical nanoaggregates in an aqueous medium. These nanoaggregates demonstrated strong antibacterial and anticancer activities. Mechanistic studies indicate that Ir-NH2 disrupts and depolarizes the bacterial membrane, thereby facilitating the eradication of bacterial cells without the significant risk of resistance development against Staphylococcus aureus (S. aureus). Subsequent fluorescence imaging demonstrated that the heparin-conjugated Ir-NH2 complex (HP-Ir-NH2) specifically targets bacterial cells, even in the presence of erythrocytes and mammalian cells. Thus, the synthesised iridium complex holds theragnostic potential and advances the emerging paradigm of coordination-driven metalloantibiotics, underscoring the potential of iridium-based complexes as new frontiers in antibacterial and fluorescence-based selective bacterial imaging agents.