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.