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<p>Red, far red, or near-infrared photoswitchable drugs offer immense photo-pharmacological advantages due to the higher light penetration through the skin. Such photoactivation is achieved using processes such as two- and three-photon absorption, excited-state absorption, and triplet-triplet annihilation upconversion, which require higher photon fluences (W to kW cm<sup>−2</sup>) than the resilience constraints of skin (200 mW cm<sup>−2</sup>). Herein, a generalized approach of <i>cis</i>-to-<i>trans</i> photoisomerization of azobenzenes is demonstrated via triplet sensitization with NIR-I illumination (850 nm) of a new Zn-octa-substituted phthalocyanine photosensitizer, in aqueous medium at 2.62 mW cm<sup>−2</sup>. The approach is applied to control the heart rate of a frog tadpole via <i>cis</i>-to-<i>trans</i> photoisomerization of an azobenzene-functionalized muscarinic acetylcholine receptor M<sub>2</sub> agonist in the phototherapeutic window (730 nm excitation: 42 mW cm<sup>−2</sup>). This advance highlights a powerful photo-pharmacological strategy for modulation of in vivo activity at 2-4 orders of magnitude lower photon fluences of NIR light compared to established methods.</p>

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Noninvasive cardiac modulation via triplet-sensitized photoswitching in the phototherapeutic window

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月10日

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  • Lukas Naimovičius,
  • Mila Miroshnichenko,
  • Ekin Opar,
  • Helen Hölzel,
  • Masa-aki Morikawa,
  • Nobuo Kimizuka,
  • Manvydas Dapkevičius,
  • Justas Lekavičius,
  • Edvinas Radiunas,
  • Karolis Kazlauskas,
  • Víctor Cilleros-Mañé,
  • Fabio Riefolo,
  • Carlo Matera,
  • Kevser Harmandar,
  • Masahiko Taniguchi,
  • Fabienne Dumoulin,
  • Jonathan S. Lindsey,
  • Pankaj Bharmoria,
  • Pau Gorostiza,
  • Kasper Moth-Poulsen

摘要

Red, far red, or near-infrared photoswitchable drugs offer immense photo-pharmacological advantages due to the higher light penetration through the skin. Such photoactivation is achieved using processes such as two- and three-photon absorption, excited-state absorption, and triplet-triplet annihilation upconversion, which require higher photon fluences (W to kW cm−2) than the resilience constraints of skin (200 mW cm−2). Herein, a generalized approach of cis-to-trans photoisomerization of azobenzenes is demonstrated via triplet sensitization with NIR-I illumination (850 nm) of a new Zn-octa-substituted phthalocyanine photosensitizer, in aqueous medium at 2.62 mW cm−2. The approach is applied to control the heart rate of a frog tadpole via cis-to-trans photoisomerization of an azobenzene-functionalized muscarinic acetylcholine receptor M2 agonist in the phototherapeutic window (730 nm excitation: 42 mW cm−2). This advance highlights a powerful photo-pharmacological strategy for modulation of in vivo activity at 2-4 orders of magnitude lower photon fluences of NIR light compared to established methods.