Transcytotic transportation of size-controlled nanocarriers into dystrophic skeletal muscle leads to therapeutic outcome in mice.

ABSTRACT: Duchenne Muscular Dystrophy (DMD) is a lethal muscle-wasting disorder with limited therapeutic options. Although nano drug delivery offers promise, the biodistribution and access routes to dystrophic muscle remain poorly understood. Here we show that intravenously administered mesoporous silica nanoparticle (MSNP) carriers exhibit striking size-dependent biodistribution in male DMD mice. Small nanocarriers (50~100 nm) efficiently accumulate in skeletal muscle while avoiding hepatic and splenic sequestration, outperforming larger particles (200~300 nm). Importantly, we uncover that endothelial transcytosis, not passive vascular leakage, is the dominant and previously unrecognized route by which nanocarriers access dystrophic muscles. Further, we encapsulate tamoxifen, a repurposed drug, int

SUBMITTER: Liu X 

PROVIDER: S-EPMC12714731 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature