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Updated: Jan 8, 2026
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
Near-Infrared Triggered Anion Transport Induces Cancer Cell Death
Manzoor Ahmad1, Ríona M Devereux1, Angela J Russell1,2
1Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
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.
Insights
Researchers developed novel near-infrared (NIR) light-activated anionophores for targeted cancer therapy. These photo-responsive molecules enable controlled ion transport, offering a promising alternative to current photodynamic therapies.
Area of Science:
- Supramolecular Chemistry
- Chemical Biology
- Nanomedicine
Background:
- Artificial transmembrane anion carriers show promise in medicine, particularly as anticancer agents.
- Stimuli-responsive systems offer targeted activation, but photo-activated ionophores often suffer from poor tissue penetration and cytotoxicity due to UV light triggers.
- Near-infrared (NIR) light offers advantages for spatiotemporal control and remote activation in biological systems.
Purpose of the Study:
- To develop novel photo-responsive anionophores activated by NIR light for targeted biological applications.
- To investigate the mechanism of NIR-triggered anion transport using dynamic hydrogen bonding.
- To evaluate the potential of these NIR-activated anionophores as a therapeutic strategy against cancer.
Main Methods:
- Design and synthesis of BODIPY-caged photo-responsive anionophores utilizing a 4-hydroxyisophthalamide motif.
- Investigation of NIR light-induced decaging and subsequent anion binding and transport.
- Anion transport experiments in vesicles and cell-based assays to assess efficacy and cytotoxicity.
Main Results:
- BODIPY-caged anionophores were successfully synthesized and demonstrated NIR light-triggered activation (730 nm).
- Efficient off-on activation profiles for anion transport were observed in vesicle experiments.
- NIR decaging induced turn-on transmembrane chloride transport in cancer cells, leading to a dose-dependent decrease in cell viability.
Conclusions:
- NIR-activated photo-responsive anionophores offer a viable strategy for spatiotemporal control of ion transport.
- These novel anionophores show significant potential as an alternative to existing photodynamic therapies for cancer treatment.
- The developed system demonstrates effective cancer cell killing via controlled chloride transport upon NIR irradiation.
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