Illuminating apoptosis: Visible light-activated chloride carrier for chloride transport and cell death

Abstract

Synthetic chloride carriers are known to induce chloride-mediated apoptosis inside cancer cells. One of the main disadvantages is the unfavorable cytotoxicity towards healthy cells due to the lack of selectivity. The use of stimuli, such as light, enzymes, ligands, etc., has enabled the selective activation of these systems in cancer cells. Light, notably, is a significant stimulus that has been utilized due to its excellent spatiotemporal control, remote addressability, and low cytotoxicity. However, previously reported photoresponsive systems require UV radiation for their activation, which has low tissue penetration and can lead to phototoxic cell damage or death. Herein, we report the 3-substituted indole-2-carboxamide ion carriers and their o-nitrobenzyl (ONB) linked procarriers. The incorporation of the electron-donating substituents to the ONB photocleavable group leads to a significant red shift in the absorption wavelength, and for N,N-dimethyl-based procarrier, the absorbance peak extends up to 500 nm. Eventually, all the synthesized procarriers were photoactivated inside MCF-7 cancer cells at 400 nm electromagnetic radiation, and the N,N-dimethyl-based procarrier was also photoactivated at 450 nm. This photoactivation at the higher wavelength of electromagnetic radiation is highly desirable for its practical biological applications.