Photocatalytic Nitroaromatic Prodrug Activation by Functionalized Gold Nanoclusters

Photocatalytic activation of prodrugs for killing cancer cells is an attractive alternative phototherapy to photodynamic therapy that typically relies on the supply of oxygen. Although prodrugs are widely developed, few other than Pt(IV) complexes are studied for photocatalytic activation. Herein, we report the photocatalytic reduction of nitrobenzene to aniline, an important chemical conversion for a large class of nitroaromatic prodrugs in cancer therapy that was previously limited to only enzyme-catalyzed activation. The carefully designed photocatalyst is a photosensitizer (PS)-functionalized gold nanocluster (Au NC) (abbreviated as Au-PS) in which a ruthenium coordination compound as the PS is covalently linked to the glutathione-ligated Au NC surface. Visible light excitation of the photocatalyst reduces nitrobenzene to aniline with 100% selectivity. The remarkably high selectivity is attributed to the specific catalytic nature of the reduced Au NC from photoinduced charge separation within the Au-PS analyzed by time-resolved absorption spectroscopy. In vitro experiments show that the nitroaromatic prodrug 5-(ziridin-1-yl)-2,4-dinitrobenzamide (CB1954) induces significant cytotoxicity in the presence of the Au-PS and light under hypoxia. The photocatalytic nitroaromatic prodrug activation by the Au-PS provides an alternative approach in the category of photochemotherapy to confront hypoxic cancer cells.