Pillararene-based AIE-active metallacycle for efficient eradication of antibiotic-resistant bacteria

The development of advanced antibacterial materials to combat multidrug-resistant pathogens remains a significant challenge in the healthcare sector. Herein, we report the design and synthesis of a novel pillar[5]arene-based platinum metallacycle (P5Pt) specifically engineered to combat multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). The obtained metallacycle serves as a host molecule that can bind with an ethylene glycol-linked bis-biotin diester linker, resulting in a water-soluble supramolecular nanosystem (P5Pt-Bio). Both P5Pt and P5Pt-Bio demonstrate remarkable efficacy against drug-resistant bacteria, particularly MRSA, with minimum inhibitory concentrations of 3.1 μM for P5Pt-Bio. Mechanistic investigations, including scanning electron microscopy and protein leakage assays, reveal significant disruption of bacterial membranes, ultimately leading to bacterial cell death. Notably, P5Pt-Bio displays excellent biocompatibility with human keratinocyte cells. These findings underscore the potential of pillar[5]arene-based supramolecular nanosystems as versatile platforms for antibacterial applications.