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

Labrak, Yasmine [UCL] Heurtault, Béatrice Frisch, Benoît Saulnier, Patrick Lepeltier, Elise Miron, Veronique E Muccioli, Giulio [UCL] des Rieux, Anne [UCL] et al.[show all]

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.