PT - JOURNAL ARTICLE AU - Miragoli, Michele AU - Ceriotti, Paola AU - Iafisco, Michele AU - Vacchiano, Marco AU - Salvarani, Nicolò AU - Alogna, Alessio AU - Carullo, Pierluigi AU - Ramirez-Rodríguez, Gloria Belén AU - Patrício, Tatiana AU - Esposti, Lorenzo Degli AU - Rossi, Francesca AU - Ravanetti, Francesca AU - Pinelli, Silvana AU - Alinovi, Rossella AU - Erreni, Marco AU - Rossi, Stefano AU - Condorelli, Gianluigi AU - Post, Heiner AU - Tampieri, Anna AU - Catalucci, Daniele TI - Inhalation of peptide-loaded nanoparticles improves heart failure AID - 10.1126/scitranslmed.aan6205 DP - 2018 Jan 17 TA - Science Translational Medicine PG - eaan6205 VI - 10 IP - 424 4099 - http://stm.sciencemag.org/content/10/424/eaan6205.short 4100 - http://stm.sciencemag.org/content/10/424/eaan6205.full AB - Nanoparticles can be useful for imaging and drug delivery but generally require intravenous injection to reach their targets. Miragoli et al. delivered nanoparticles carrying peptides to the heart by inhalation rather than injection. The inhaled particles reached the heart faster than injected particles and were taken up by cardiomyocytes to improve cardiac function in a mouse model of diabetic cardiomyopathy. In healthy pigs, inhaled particles were also found in heart tissue, suggesting that this minimally invasive method of targeted cardiac delivery could potentially translate to humans.Peptides are highly selective and efficacious for the treatment of cardiovascular and other diseases. However, it is currently not possible to administer peptides for cardiac-targeting therapy via a noninvasive procedure, thus representing scientific and technological challenges. We demonstrate that inhalation of small (<50 nm in diameter) biocompatible and biodegradable calcium phosphate nanoparticles (CaPs) allows for rapid translocation of CaPs from the pulmonary tree to the bloodstream and to the myocardium, where their cargo is quickly released. Treatment of a rodent model of diabetic cardiomyopathy by inhalation of CaPs loaded with a therapeutic mimetic peptide that we previously demonstrated to improve myocardial contraction resulted in restoration of cardiac function. Translation to a porcine large animal model provides evidence that inhalation of a peptide-loaded CaP formulation is an effective method of targeted administration to the heart. Together, these results demonstrate that inhalation of biocompatible tailored peptide nanocarriers represents a pioneering approach for the pharmacological treatment of heart failure.