Peptide mediated targeted delivery of gold nanoparticles into the demyelination site ameliorates myelin impairment and gliosis

Drug development for multiple sclerosis (MS) clinical management focuses on both neuroprotection and repair strategies, and is challenging due to low permeability of the blood-brain barrier, off-target distribution, and the need for high doses of drugs. The changes in the extracellular matrix have been documented in MS patients. It has been shown that the expression of nidogen-1 increases in MS lesions. Laminin forms a stable complex with nidogen-1 through a heptapeptide which was selected to target the lesion area in this study. Here we showed that the peptide binding was specific to the injured area following lysophosphatidylcholine (LPC) induced demyelination. In vivo data showed enhanced delivery of the peptide-functionalized gold nanoparticles (Pep-GNPs) to the lesion area. In addition, Pep-GNPs administration significantly enhanced myelin content and reduced astrocyte/microglia activation. Results demonstrated the possibility of using this peptide to target and treat lesions in patients suffering from MS.