Aptamer-conjugated gold nanoparticles enable oligonucleotide delivery into muscle stem cells to promote regeneration of dystrophic muscles

Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, ba...

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Bibliographic Details
Published in:Nature communications 2025-01, Vol.16 (1), p.577
Main Authors: Millozzi, Francesco, Milán-Rois, Paula, Sett, Arghya, Delli Carpini, Giovanni, De Bardi, Marco, Gisbert-Garzarán, Miguel, Sandonà, Martina, Rodríguez-Díaz, Ciro, Martínez-Mingo, Mario, Pardo, Irene, Esposito, Federica, Viscomi, Maria Teresa, Bouché, Marina, Parolini, Ornella, Saccone, Valentina, Toulmé, Jean-Jacques, Somoza, Álvaro, Palacios, Daniela
Format: Article
Language:English
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Aptamers
Biocompatibility
Conjugation
Duchenne's muscular dystrophy
Dystrophy
Gold
Humanities and Social Sciences
Immunogenicity
miRNA
multidisciplinary
Muscles
Muscular dystrophy
Nanoparticles
Oligonucleotides
Regeneration
Satellite cells
Science
Science (multidisciplinary)
Skeletal muscle
Stem cells
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Description
Summary:Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, based on gold nanoparticles, that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs conjugation to an aptamer against α7/β1 integrin dimers directs either local or systemic delivery of microRNA-206 to MuSCs, thereby promoting muscle regeneration and improving muscle functionality, in a mouse model of Duchenne Muscular Dystrophy. We show here that this platform is biocompatible, non-toxic, and non-immunogenic, and it can be easily adapted for the release of a wide range of therapeutic oligonucleotides into diseased muscles. Lack of muscle stem cell targeting limits the treatment of muscular dystrophies. Here, the authors describe a platform based on functionalized gold nanoparticles that allows selective delivery of therapeutic oligonucleotides and promotes skeletal muscle regeneration.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-55223-9