A Cell Membrane Targeting Molybdenum-Iodine Nanocluster:Rational Ligand Design toward Enhanced Photodynamic Activity br

he development of singlet oxygen photosensitizers, whichtarget specific cellular organelles, constitutes a pertinent endeavor to optimizethe efficiency of photodynamic therapy. Targeting of the cell membraneeliminates the need for endocytosis of drugs that can lead to toxicity,intracellular degradation, or drug resistance. In this context, we utilizedcopper-free click chemistry to prepare a singlet oxygen photosensitizingcomplex, made of a molybdenum-iodine nanocluster stabilized by triazolateapical ligands. In phosphate-buffered saline, the complex formed nano-aggregates with a positive surface charge due to the protonatable aminefunction of the apical ligands. These nanoaggregates targeted cell membranesand caused an eminent blue-light phototoxic effect against HeLa cells atnanomolar concentrations, inducing apoptotic cell death, while having no dark toxicity at physiologically relevant concentrations.The properties of this complex were compared to those of a negatively charged parent complex to highlight the dominant effect ofthe nature of apical ligands on biological properties of the nanocluster. These two complexes also exerted (photo)antibacterial effectson several pathogenic strains in the form of planktonic cultures and biofilms. Overall, we demonstrated that the rational design ofapical ligands toward cell membrane targeting leads to enhanced photodynamic efficiency.