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

2025; Nature Portfolio; Volume: 16; Issue: 1 Linguagem: Inglês

10.1038/s41467-024-55223-9

2041-1723

Francesco Millozzi, Paula Milán-Rois, Arghya Sett, Giovanni Delli Carpini, Marco De Bardi, Miguel Gisbert-Garzarán, Martina Sandonà, Ciro Rodríguez Díaz, Mario Martínez‐Mingo, Irene Pardo, Federica Esposito, Maria Teresa Viscomi, Marina Bouché, Ornella Parolini, Valentina Saccone, Jean‐Jacques Toulmé, Álvaro Somoza, Daniela Palacios,

Extracellular vesicles in disease

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.