Impact of anti-PDGFRα antibody surface functionalization on LNC uptake by oligodendrocyte progenitor cells

Int J Pharm. 2022 Apr 25:618:121623. doi: 10.1016/j.ijpharm.2022.121623. Epub 2022 Feb 26.

Abstract

Impairment of oligodendrocyte progenitor cell (OPC) differentiation into oligodendrocytes and chronic inflammation are key determinants of poor remyelination observed in diseases such as multiple sclerosis. For many pro-myelinating molecules, the therapeutic potential is hindered by poor solubility or limited access to the targeted cells. A promising approach to improve the delivery of those molecules to OPC is to encapsulate them in functionalized Lipid Nanocapsules (LNC). We aimed to develop the first OPC-targeting LNC, by grafting an anti-PDGFRα antibody on the surface of the LNC using several strategies and evaluating the interaction with PDGFRα via ELISA. We found that only site-selective click-chemistry grafting maintained anti-PDGFRα/PDGFRα association, which was confirmed in vitro on primary rat OPC. In conclusion, we demonstrated that it was possible to produce anti-PDGFRα functionalized LNC, we confirmed the antibody's ability to recognize its receptor after grafting and we optimized techniques to characterize antibody functionalized LNC.

Keywords: Central nervous system; Multiple sclerosis; Nanomedicines; Remyelination; Surface modification; lipid nanoparticles.

MeSH terms

  • Animals
  • Cell Differentiation
  • Nanocapsules*
  • Oligodendrocyte Precursor Cells* / metabolism
  • Oligodendroglia / metabolism
  • Rats
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Remyelination*

Substances

  • Nanocapsules
  • Receptor, Platelet-Derived Growth Factor alpha