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Neurochem Res ; 45(11): 2732-2748, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32910302

ABSTRACT

Promoting remyelination in multiple sclerosis is important to prevent axon degeneration, given the lack of curative treatment. Although some growth factors improve this repair, unspecific delivery to cells and potential side effects limit their therapeutic use. Thus, NFL-TBS.40-63 peptide (NFL)-known to enter specifically myelinating oligodendrocytes (OL)-was used to vectorize 100 nm diameter lipid nanoparticles (LNC), and the ability of NFL-LNC to specifically target OL from newborn rat brain was assessed in vitro. Specific uptake of DiD-labeled NFL-LNC by OL characterized by CNP and myelin basic protein was observed by confocal microscopy, as well as DiD colocalization with NFL and with Rab5-a marker of early endosomes. Unvectorized LNC did not significantly penetrate OL and there was no uptake of NFL-LNC by astrocytes. Canonical maturation of OL which extended compacted myelin-like membranes was observed by transmission electron microscopy in cells grown up to 9 days with NFL-LNC. Endocytosis of NFL-LNC appeared to depend on several pathways, as demonstrated by inhibitors. In addition, vectorized NFL-LNC adsorbed on neurotrophin-3 (NT-3) potentiated the proremyelinating effects of NT-3 after demyelination by lysophosphatidyl choline, allowing noticeably decreasing NT-3 concentration. Our results if they were confirmed in vivo suggest that NFL-vectorized LNC appear safe and could be considered as putative carriers for specific drug delivery to OL in order to increase remyelination.


Subject(s)
Nanoparticles/chemistry , Neurofilament Proteins/pharmacology , Neuroprotective Agents/pharmacology , Neurotrophin 3/metabolism , Oligodendroglia/drug effects , Peptide Fragments/pharmacology , Remyelination/drug effects , Amino Acid Sequence , Animals , Animals, Newborn , Astrocytes/drug effects , Cell Differentiation/drug effects , Drug Carriers/chemistry , Endocytosis , Humans , Lipids/chemistry , Lysophosphatidylcholines/pharmacology , Myelin Sheath/drug effects , Neurofilament Proteins/metabolism , Neuroprotective Agents/metabolism , Peptide Fragments/metabolism , Rats, Wistar
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