Polymeric nanoparticles functionalized with muscle-homing peptides for targeted delivery of phosphatase and tensin homolog inhibitor to skeletal muscle

Acta Biomater. 2020 Dec:118:196-206. doi: 10.1016/j.actbio.2020.10.009. Epub 2020 Oct 11.

Abstract

Phosphatase and tensin homolog (PTEN) antagonizes muscle growth and repair, and inhibition of PTEN has been shown to improve the pathophysiology and dystrophic muscle function in a mouse model of Duchenne muscular dystrophy (DMD). However, conventional pharmacological delivery of PTEN inhibitors carries a high risk of off-target side effects in other non-muscle organs due to broad targeting spectrums. Here we report a muscle-targeted nanoparticulate platform for cell-specific delivery of a PTEN inhibitor. Poly(lactide-co-glycolide)-b-poly(ethylene glycol) nanoparticles (NPs) are functionalized with a muscle-homing peptide M12 to promote the selective uptake by muscle cells/tissue in vitro and in vivo. Moreover, the NPs are formulated to slowly release the PTEN inhibitor, preventing cytotoxicity associated with direct exposure to the drug and facilitating sustained inhibition of PTEN. This advanced delivery approach taking advantages of polymeric nanomaterials and muscle-homing peptides opens a new avenue for the development of long-term therapeutic strategies in DMD treatment.

Keywords: Duchenne muscular dystrophy; Muscle-homing peptides; PTEN signaling; Polymeric nanoparticles; Targeted drug delivery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Delivery Systems*
  • Mice
  • Muscle, Skeletal*
  • Nanoparticles*
  • PTEN Phosphohydrolase / antagonists & inhibitors*
  • Peptides
  • Polyethylene Glycols

Substances

  • Peptides
  • Polyethylene Glycols
  • PTEN Phosphohydrolase