Cardiovascular (CV) disease is the leading cause of mortality and morbidity worldwide, with an increasing incidence in the aging population and a huge socio-economical impact. Heart failure (HF), the common end point of virtually all CV disorders, displays the greatest negative impact on quality of life, leading to the disruption of daily management and increasing dependence on care-givers. Unfortunately, an effective pharmacological treatment is currently lacking, as it is not possible to reverse disease progression; as a consequence, the long-term survival remains poor, and heart transplantation is the only possibility for end-stage HF patients. Thus, a breakthrough approach to preserve or, at least, restore cardiovascular function and to rescue systemic blood perfusion is urgently required. LION-HEARTED will demonstrate a novel optoceutic platform, based on synergistic combination of light and organic nanotechnology, to restore cardiac function and vascularization, by modulating fate and proliferation of main cardiovascular cell types. Optical modulation will provide unprecedented spatio-temporal resolution, lower invasiveness, and higher selectivity in respect to traditional electrical and pharmaceutical control methods. Organic semiconductors will act as efficient, highly biocompatible phototransducers, able to trigger biological pathways relevant to cardiac repair, with a minimally invasive and gene-less approach. This strategy will circumvent most of the hurdles currently limiting the efficacy of molecular therapies, by directly stimulating the reparative phenotype of resident cardiac progenitors, cardiomyocytes, and of circulating endothelial cells homing towards the heart after an ischemic insult. The final outcome will be the realization of a proof of concept, implantable device for enhancing cardiac repair in ischemic, aneurysm and stenosis in vivo animal models.