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Updated: Aug 12, 2025
Two-Photon-Based Photoactivation in Live Zebrafish Embryos
Published on: December 24, 2010
Two-photon activated precision molecular photosensitizer targeting mitochondria
Inês F A Mariz1, Sandra N Pinto2,3, Ana M Santiago1
1Centro de Química Estrutural (CQE) and Institute of Molecular Sciences (IMS), Instituto Superior Técnico, Universidade de Lisboa, 1049-001, Lisboa, Portugal.
Abstract:
Mitochondria metabolism is an emergent target for the development of novel anticancer agents. It is amply recognized that strategies that allow for modulation of mitochondrial function in specific cell populations need to be developed for the therapeutic potential of mitochondria-targeting agents to become a reality in the clinic. In this work, we report dipolar and quadrupolar quinolizinium and benzimidazolium cations that show mitochondria targeting ability and localized light-induced mitochondria damage in live animal cells. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The dipolar compounds could be excited in the NIR due to a high two-photon brightness while exhibiting emission in the red part of the visible spectra (600-700 nm). Interaction with the mitochondria leads to an unexpected blue-shift of the emission of the far-red emitting compounds, which we assign to emission from the locally excited state. Interaction and possibly aggregation at the mitochondria prevents access to the intramolecular charge transfer state responsible for far-red emission.
Insights
Novel anticancer agents targeting mitochondria metabolism were developed. These compounds induce targeted cell death via light-activated mitochondrial damage, showing promise for precision cancer therapy.
Area of Science:
- Biochemistry
- Cell Biology
- Medicinal Chemistry
Background:
- Mitochondria metabolism is a key target for novel anticancer drug development.
- Targeted modulation of mitochondrial function is crucial for effective clinical application of mitochondria-targeting agents.
Purpose of the Study:
- To develop novel mitochondria-targeting photosensitizers for cancer therapy.
- To investigate the mechanism of light-induced mitochondrial damage and cell death.
Main Methods:
- Synthesis of dipolar and quadrupolar quinolizinium and benzimidazolium cations.
- Evaluation of mitochondria targeting ability in live animal cells.
- Assessment of light-induced mitochondrial damage and cell death under two-photon excitation in the Near-infrared (NIR) spectrum.
Main Results:
- The synthesized cations demonstrated effective mitochondria targeting.
- Near-infrared (NIR) two-photon excitation induced localized mitochondrial damage and subsequent cell death.
- Dipolar compounds exhibited high two-photon brightness and red-shifted emission, with a blue-shift upon mitochondrial interaction.
Conclusions:
- Azonia/azolium aromatic heterocycles show potential as precision photosensitizers for cancer treatment.
- Targeted disruption of mitochondrial potential can be achieved using NIR light-activated compounds.
- Mitochondrial interaction influences dye emission properties, suggesting localized excitation states.
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