In vivo optical induction of INaL by photoactivation of AaH-II peptide in beating heart using wireless implantable device
Precise spatiotemporal control of pharmacological compounds in cardiac tissue remains an unmet challenge. Systemic drug administration poorly reproduces the localized and transient nature of cardiac events. Photopharmacology, in which light controls drug activity, offers a compelling solution, but its translation to the beating heart requires wireless light delivery to a moving, soft, and electrically active organ. Here, we demonstrate the first in vivo use of a wireless device to photoactivate a peptide that modulates cardiac excitability. Using a flexible, battery-free implantable optoelectronic device, we achieved light-triggered uncaging of AaH-II*, a natural peptide that enhances the late sodium current. We first validated the caged peptide in vitro and ex vivo, showing that caging suppresses its activity and that UV illumination rapidly restores it. In vivo, wireless photoactivation produced a clear modulation of cardiac electrical activity, as monitored by electrocardiography. This work establishes device-based peptide photomodulation as a strategy for remote, temporally controlled pharmacological intervention in the heart. More broadly, it provides a new platform for probing cardiac excitability and developing region-targeted therapies.
Authors
- Flavien Charpentier (ORCID: https://orcid.org/0000-0002-5057-0998)
- Agnès Hivonnait (ORCID: https://orcid.org/0009-0003-5626-6836)
- Philipp Gutruf (ORCID: https://orcid.org/0000-0002-7183-7268)
- Romain Capoulade (ORCID: https://orcid.org/0000-0002-7233-7409)
- Antoine Persello (ORCID: https://orcid.org/0000-0002-4722-9422)
- Michel MDW DE WAARD (ORCID: https://orcid.org/0000-0002-2782-9615)
- Edith Bigot
- Virginie Aillerie (ORCID: https://orcid.org/0000-0003-2765-2626)
- Pascal Aumond
- Hugo Millet (ORCID: https://orcid.org/0009-0006-5172-756X)
- Claude Zoukimian
- Jérôme Montnach (ORCID: https://orcid.org/0000-0001-5100-5571)
- Rémy Béroud
- Matthias Dereli (ORCID: https://orcid.org/0009-0005-8297-7695)
- Maureen Choteau‐Bodor (ORCID: https://orcid.org/0009-0004-8347-3440)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Arizona (US)
- Inserm (FR)
- Centre Hospitalier Universitaire de Nantes (FR)
- OPX Biotechnologies (United States) (US)
- Centre d'Investigation Clinique de Nantes (FR)
- Institut du Thorax (FR)
- Université de Nantes (FR)
- Nantes Université (FR)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-10-28
- DOI
- https://doi.org/10.64898/2026.10.27.761894
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- preprint
Funders
- Infrastructures en Biologie Santé et Agronomie
- Agence Nationale de la Recherche
- Fondation Leducq
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Conseil Régional des Pays de la Loire