RT Journal Article SR Electronic T1 Inhalation of peptide-loaded nanoparticles improves heart failure JF Science Translational Medicine FD American Association for the Advancement of Science SP eaan6205 DO 10.1126/scitranslmed.aan6205 VO 10 IS 424 A1 Miragoli, Michele A1 Ceriotti, Paola A1 Iafisco, Michele A1 Vacchiano, Marco A1 Salvarani, Nicolò A1 Alogna, Alessio A1 Carullo, Pierluigi A1 Ramirez-Rodríguez, Gloria Belén A1 Patrício, Tatiana A1 Esposti, Lorenzo Degli A1 Rossi, Francesca A1 Ravanetti, Francesca A1 Pinelli, Silvana A1 Alinovi, Rossella A1 Erreni, Marco A1 Rossi, Stefano A1 Condorelli, Gianluigi A1 Post, Heiner A1 Tampieri, Anna A1 Catalucci, Daniele YR 2018 UL http://stm.sciencemag.org/content/10/424/eaan6205.abstract 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.