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

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 () and Kasper Moth-Poulsen ()
Additional contact information
Lukas Naimovičius: Bellaterra
Mila Miroshnichenko: Bellaterra
Ekin Opar: The Barcelona Institute of Science and Technology
Helen Hölzel: Eduard Maristany 10–14
Masa-aki Morikawa: Kyushu University
Nobuo Kimizuka: Kyushu University
Manvydas Dapkevičius: Vilnius University
Justas Lekavičius: Vilnius University
Edvinas Radiunas: Vilnius University
Karolis Kazlauskas: Vilnius University
Víctor Cilleros-Mañé: The Barcelona Institute of Science and Technology
Fabio Riefolo: The Barcelona Institute of Science and Technology
Carlo Matera: The Barcelona Institute of Science and Technology
Kevser Harmandar: Biomedical Engineering Department
Masahiko Taniguchi: North Carolina State University
Fabienne Dumoulin: Biomedical Engineering Department
Jonathan S. Lindsey: North Carolina State University
Pankaj Bharmoria: Bellaterra
Pau Gorostiza: The Barcelona Institute of Science and Technology
Kasper Moth-Poulsen: Bellaterra

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-61301-3

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