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.