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Elucidating the Inability of Functionalized Nanoparticles to Cross the Blood–Brain Barrier and Target Specific Cells in Vivo

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posted on 31.05.2019, 00:00 by Priya S. R. Naidu, Nikolas Gavriel, Chloe G. G. Gray, Carole A. Bartlett, Lillian M. Toomey, Jessica A. Kretzmann, Diana Patalwala, Terence McGonigle, Eleanor Denham, Charmaine Hee, Diwei Ho, Nicolas L. Taylor, Marck Norret, Nicole M. Smith, Sarah A. Dunlop, K. Swaminathan Iyer, Melinda Fitzgerald
The adsorption of serum proteins on the surface of nanoparticles (NPs) delivered into a biological environment has been known to alter NP surface properties and consequently their targeting efficiency. In this paper, we use random copolymer (p­(HEMA-ran-GMA))-based NPs synthesized using 2-hydroxyethyl methacrylate (HEMA) and glycidyl methacrylate (GMA). We show that serum proteins bind to the NP and that functionalization with antibodies and peptides designed to facilitate NP passage across the blood–brain barrier (BBB) to bind specific cell types is ineffective. In particular, we use systematic in vitro and in vivo analyses to demonstrate that p­(HEMA-ran-GMA) NPs functionalized with HIV-1 trans-activating transcriptor peptide (known to cross the BBB) and α neural/glial antigen 2 (NG2) (known for targeting oligodendrocyte precursor cells (OPCs)), individually and in combination, do not specifically target OPCs and are unable to cross the BBB, likely due to the serum protein binding to the NPs.

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