Near‐Infrared Triggered Anion Transport Induces Cancer Cell Death

TL;DR

This paper introduces a new light-activated system that uses near-infrared light to trigger anion transport and kill cancer cells.

Contribution

The study introduces a novel NIR-activated anionophore using BODIPY-caging and hydrogen bonding for controlled ion transport and cancer cell death.

Findings

NIR decaging activates anion transport in vesicles with efficient on-off profiles.

NIR-activated anionophores induce chloride influx and dose-dependent cancer cell death.

The system shows potential as an alternative to existing photodynamic cancer therapies.

Abstract

Artificial transmembrane anion carriers have shown potential in biological research and medicine, such as chemotherapeutics to treat channelopathies and anticancer agents. Stimuli‐responsive systems, controlled by triggers such as light, pH, redox, enzymes, or membrane potential, offer the potential for targeted activation. Photoactivation of ion transport is particularly advantageous due to the possibility of achieving spatiotemporal control, remote addressability, and reduced cytotoxicity. However, poor tissue penetration and undesired cytotoxicity are significant drawbacks to many photo‐activated ionophores reported to date, which are mostly triggered by UV or violet light. Here, we report BODIPY‐caged photo‐responsive anionophores activated with NIR light, which utilize dynamic hydrogen bonding interactions of a 4‐hydroxyisophthalamide motif. Caging of the hydroxyl group of the anionophore with BODIPY‐photocages locks the amide proton through six‐membered intramolecular hydrogen bonding, rendering it unavailable for anion recognition and transport. Decaging with 730 nm NIR irradiation reverses the hydrogen bonding pattern to switch on binding, with efficient off‐on activation profiles observed in anion transport experiments in vesicles. Analogous experiments in cancer cells revealed turn‐on transmembrane chloride transport and a dramatic, dose‐dependent decrease in cell viability following NIR decaging of the anionophore, demonstrating the potential for NIR‐triggered ionophores as an alternative to existing photodynamic therapies for cancer.

Photo‐responsive transmembrane anion transporters that are activated with NIR light are reported. Experiments in cancer cells revealed that NIR activation of the ionophore triggered near‐IR light‐dependent chloride influx and triggered cell death.

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