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[en] 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 (Exomyo). Effective nanocarriers are realized by immobilizing the Exomyo onto ferromagnetic nanotubes to achieve controlled delivery and localization of Exomyo to skeletal muscles by systemic injection using an external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exomyo 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.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Disciplines :
Biotechnology
Author, co-author :
VILLA, Chiara; UNIMI - Università degli Studi di Milano [IT] > Stem Cell Laboratory, Dino Ferrari Center, Department of Pathophysiology and Transplantation
SECCHI, Valeria; Università degli Studi di Milano Bicocca [IT] > Department of Materials Science
MACCHI, Mirco ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science
TRIPODI, Luana; UNIMI - Università degli Studi di Milano [IT] > Stem Cell Laboratory, Dino Ferrari Center, Department of Pathophysiology and Transplantation
TROMBETTA, Elena; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy > Flow Cytometry Service, Clinical Pathology
ZAMBRONI, Desiree; San Raffaele Scientific Institute – OSR, Milan, Italy > Advanced Light and Electron Microscopy Bioimaging Center ALEMBIC
PADELLI, Francesco; IRCCS Foundation Neurological Institute ‘Carlo Besta’, Milan, Italy > Department of Neuroradiology
MAURI, Michele; University of Milano Bicocca, Milan, Italy > Department of Materials Science
MOLINARO, Monica; UNIMI - Università degli Studi di Milano [IT] > Stem Cell Laboratory, Dino Ferrari Center, Department of Pathophysiology and Transplantation
ODDONE, Rebecca; UNIMI - Università degli Studi di Milano [IT] > Stem Cell Laboratory, Dino Ferrari Center, Department of Pathophysiology and Transplantation
FARINI, Andrea; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy > Neurology Unit
DE PALMA, Antonella; National Research Council of Italy > Proteomics and Metabolomics Unit > Institute for Biomedical Technologies, ITB-CNR, Segrate, Milan, Italy ; ITB-CNR, Elixir, Milan, Italy > Clinical Proteomics Laboratory, > CNR.Biomics Infrastructure,
SANTARELLI, Federica; UNIMI - Università degli Studi di Milano [IT] > Stem Cell Laboratory, Dino Ferrari Center, Department of Pathophysiology and Transplantation
SIMONUTTI, Roberto; Università degli Studi di Milano Bicocca [IT] > Department of Materials Science
MAURI, PierLuigi; National Research Council of Italy, Institute for Biomedical Technologies, ITB-CNR, Segrate, Milan, Italy > Proteomics and Metabolomics Unit ; ITB-CNR, CNR.Biomics Infrastructure, Elixir, Milan, Italy > Clinical Proteomics Laboratory
PORRETTI, Laura; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy > Clinical Pathology > Flow Cytometry
CAMPIONE, Marcello; NANOMIB, Nanomedicine Center, University of Milano Bicocca, Milan, Italy ; University of Milano Bicocca, Milano, Italy > Department of Earth and Environmental Sciences
AQUINO, Domenico; IRCCS Foundation Neurological Institute ‘Carlo Besta’, Milan, Italy > Department of Neuroradiology
MONGUZZI, Angelo ✱; University of Milano Bicocca, Milan, Italy > Department of Materials Science ; University of Milano Bicocca, Milan, Italy > NANOMIB, Nanomedicine Center
TORRENTE, Yvan ✱; UNIMI - Università degli Studi di Milano [IT] > Dino Ferrari Center, Department of Pathophysiology and Transplantation > Stem Cell Laboratory ; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy > Neurology Unit
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