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

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 car...

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Bibliographic Details
Published in:Acta biomaterialia 2020-12, Vol.118, p.196-206
Main Authors: Huang, Di, Yue, Feng, Qiu, Jiamin, Deng, Meng, Kuang, Shihuan
Format: Article
Language:English
Subjects:
Animals
Biocompatibility
Cytotoxicity
Drug Delivery Systems
Duchenne muscular dystrophy
Duchenne's muscular dystrophy
Dystrophy
Homing
Homology
Inhibitors
Mice
Muscle, Skeletal
Muscle-homing peptides
Muscles
Muscular dystrophy
Nanomaterials
Nanoparticles
Nanotechnology
Organs
Peptides
Phosphatase
Poly(lactide-co-glycolide)
Polyethylene glycol
Polyethylene Glycols
Polymeric nanoparticles
PTEN Phosphohydrolase - antagonists & inhibitors
PTEN protein
PTEN signaling
Side effects
Skeletal muscle
Targeted drug delivery
Tensin
Toxicity
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Summary: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. [Display omitted]
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2020.10.009