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

Authors

Millozzi F., Milán-Rois P., Sett A., Delli Carpini G., De Bardi M., Gisbert-Garzarán M., Sandonà M., Rodríguez-Díaz C., Martínez-Mingo M., Pardo I., Esposito F., Viscomi M.T., Bouché M., Parolini O., Saccone V., Toulmé J.J., Somoza Á., Palacios D.

Reference

Nature Communications, vol. 16, n° 1, art. no. 577, 2025

Description

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.

Link

doi:10.1038/s41467-024-55223-9