An Implantable Phototriggered Prodrug Depot Patch Enables Actively Programmable Drug Release for Post‐Myocardial Infarction Therapy

ABSTRACT The prolonged healing process after myocardial infarction (MI) necessitates extended pharmacotherapy. While microenvironment‐responsive implantable drug delivery systems can achieve various long‐term release patterns, they offer only passive, non‑programmable profiles. Light‐controlled strategies enable precise external regulation but face two critical barriers: the lack of integrated devices combining stable drug reservoirs with implantable light platforms, and the inherent light–release coupling of conventional phototriggered systems that necessitates continuous illumination for sustained dosing. Here, we develop an implantable phototriggered prodrug depot patch (iPDP) enabling actively programmable drug release after implantation. The iPDP fuses a phototriggered sustained‐release prodrug hydrogel (GTel‑hydrogel) and a percutaneous light‑guiding device. The prodrug GTel features a self‐immolative linker, allowing a brief optical trigger to initiate sustained, light‑independent release. The covalently conjugated prodrug ensures minimal leakage, with dose per release precisely controlled by illumination parameters (intensity/duration) as the programming code. In a rat MI model, the iPDP delivered a triple‑dose, actively programmed regimen. Compared with a single release of an equivalent total dose, this fractionated programmed strategy showed superior efficacy in improving cardiac function and suppressing inflammation. The iPDP enables post‑implantation active control from a single device, offering a promising strategy for long‐term dynamic post‐MI therapy.