To realize clinical application of antibacterial photodynamic therapy (aPDT), one of the most arduous challenges is how to render aPDT agents high selectivity against bacterial pathogens. In light of the fact that amino group‐containing lipids are rich on the outer surfaces of Gram‐positive bacteria, we herein constructed an alkynyl‐dangling ruthenium(II) polypyridine complex (Ru2) to preferentially label Staphylococcus aureus (S. aureus) and methicillin‐resistant Staphylococcus aureus (MRSA) over mammalian cells via the amino‐yne bio‐orthogonal click reaction. Thanks to the strong singlet oxygen generation ability, Ru2 could photo‐inactivate S. aureus and MRSA effectively and specifically. Phosphatidylethanolamine (PE) molecules also exist in mammalian cells but are not accessible for Ru2, leading to its poor binding/uptake and negligible cytotoxicity in the dark and upon irradiation towards mammalian cells as well as low hemolysis, all favorable for aPDT application.

Phototherapy for cancer treatment has received much attention in recent years, the compounds with multiple anticancer mechanisms upon irradiation are particularly appealing. In this work, a nitro-anthraquinone group was attached...