A near-infrared superoxide generator based on a biocompatible indene-bearing heptamethine cyanine dye†

Abstract

One of the most significant limitations of photodynamic therapy is its reduced efficacy in hypoxic microenvironments, which are typical of the majority of tumors. This work demonstrates that indolenine heptamethine cyanines with different substituents in the polymethine chain and at the terminal heterocycles are effective superoxide generators that can be activated in the near-infrared range. The introduction of an indene moiety into the polymethine chain results in a significant enhancement in photostability compared to dyes with a cyclohexene moiety or an unsubstituted polymethine chain. A hydrophilic indene-bearing heptamethine cyanine dye is shown to be efficiently internalized by Vero E6 cells and to give bright intracellular fluorescence in the 700–850 nm range. Furthermore, the dye generates superoxide anion radicals and induces severe oxidative stress in cells upon activation in the near-infrared range (∼750 nm), ultimately resulting in cell death. The capacity of heptamethine cyanines to generate a superoxide anion radical may prove advantageous for enhancing the efficacy of photodynamic therapy under hypoxic conditions.