Magnetic-field-driven targeting of exosomes modulates immune and metabolic changes in dystrophic muscle
Chiara Villa, Valeria Secchi, M. Macchi, Luana Tripodi, Elena Trombetta, Desirée Zambroni, Francesco Padelli, Michele Mauri, Monica L. Molinaro, Rebecca Oddone, Andrea Farini, Antonella De Palma, Laura Varela Pinzon, Federica Santarelli, Roberto Simonutti, Pierluigi Mauri, Laura Porretti, Marcello Campione, Domenico Aquino, Angelo Monguzzi, Yvan Torrente
Abstract
Abstract Exosomes are promising therapeutics for tissue repair and regeneration to induce and guide appropriate immune responses in dystrophic pathologies. However, manipulating exosomes to control their biodistribution and targeting them in vivo to achieve adequate therapeutic benefits still poses a major challenge. Here we overcome this limitation by developing an externally controlled delivery system for primed annexin A1 myo-exosomes (Exo myo ). Effective nanocarriers are realized by immobilizing the Exo myo onto ferromagnetic nanotubes to achieve controlled delivery and localization of Exo myo to skeletal muscles by systemic injection using an external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exo myo from these ferromagnetic nanotubes in vivo to synergistically promote beneficial muscle responses in a murine animal model of Duchenne muscular dystrophy. Our findings provide insights into the development of exosome-based therapies for muscle diseases and, in general, highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution.