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

Manzoor Ahmad1, Naveen J Roy1, Debashis Mondal1

  • 1Department of Chemistry, Indian Institute of Science Education and Research Pune, Dr Homi Bhabha Road, Pashan, Pune 411008, Maharashtra, India. ptalukdar@iiserpune.ac.in.

Insights

Researchers developed novel light-activated chloride carriers for cancer therapy. These procarriers, activated by visible light, show improved selectivity and reduced damage to healthy cells, enhancing cancer treatment potential.

Area of Science:

  • Biochemistry
  • Materials Science
  • Oncology

Background:

  • Synthetic chloride carriers induce cancer cell apoptosis but lack selectivity, harming healthy cells.
  • Light-activated systems offer spatiotemporal control but often require harmful UV radiation.
  • Existing photoresponsive systems have limitations in tissue penetration and phototoxicity.

Purpose of the Study:

  • To develop novel photoresponsive chloride carriers with enhanced selectivity for cancer treatment.
  • To shift the activation wavelength of photoresponsive systems towards the visible light spectrum.
  • To investigate the efficacy of indole-2-carboxamide derivatives as procarriers.

Main Methods:

  • Synthesis of 3-substituted indole-2-carboxamide ion carriers and their o-nitrobenzyl (ONB) linked procarriers.
  • Incorporation of electron-donating substituents to tune the absorption wavelength of ONB photocleavable groups.
  • Photoactivation studies of synthesized procarriers in MCF-7 cancer cells using visible light.

Main Results:

  • Synthesized procarriers exhibited a red shift in absorption wavelength, with one extending to 500 nm.
  • All procarriers were successfully photoactivated in MCF-7 cancer cells under 400 nm light.
  • The N,N-dimethyl-based procarrier demonstrated photoactivation at 450 nm, a higher, more biologically compatible wavelength.

Conclusions:

  • Novel indole-2-carboxamide procarriers can be activated by visible light, overcoming UV limitations.
  • The developed system shows potential for selective cancer therapy with reduced phototoxicity.
  • This advancement is crucial for the practical application of photoactivatable drugs in biological systems.

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