Lipophilic Nitrile N-Oxide for Catalyst-Free Surface Modification of Nanoemulsions as Light-Harvesting Nanoantennas

Abstract

Abstract The therapeutic and diagnostic applications of nanoemulsions (NEs) are restricted by a lack of suitable methods to modify their surfaces, specifically the surfactant-stabilized oil–water interface. Herein, we developed a modification technique using a lipophilic nitrile N-oxide compound (LipoCNO). LipoCNO-loaded NEs underwent efficient 1,3-dipolar cycloaddition with functional molecules bearing a terminal C=C or C≡C bond under mild, catalyst-free conditions at the oil–water interface, thus producing surface-functionalized NEs that could be used without purification. To exemplify the applicability of this technique, NEs encapsulating fluorescent molecules (Cy3.5LP) and LipoCNO were surface functionalized with pheophorbide a (PpA), a singlet-oxygen-generating photosensitizer. These NEs acted as light-harvesting nanoantennas, with the excitation energy gathered by Cy3.5LP in the NEs migrating to PpA on the NE surfaces via Förster resonance energy transfer. This system showed 7–18 times more efficient singlet oxygen generation than direct PpA excitation. Furthermore, PpA-functionalized dye-loaded NEs induced cancer cell death under photoillumination. These results highlight the utility of LipoCNO for functionalizing NE surfaces toward the realization of new biological applications.