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.