Abstract
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 alpha 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.
| Original language | English |
|---|---|
| Pages (from-to) | 22085-22095 |
| Number of pages | 11 |
| Journal | ACS APPLIED MATERIALS & INTERFACES |
| Volume | 11 |
| Issue number | 25 |
| DOIs | |
| Publication status | Published - 26 Jun 2019 |
Cite this
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Elucidating the inability of functionalized nanoparticles to cross the blood-brain barrier and target specific cells in vivo. / Naidu, Priya S. R.; Gavriel, Nikolas; Gray, Chloe G. G.; Bartlett, Carole A.; Toomey, Lillian M.; Kretzmann, Jessica A.; Patalwala, Diana; McGonigle, Terence; Denham, Eleanor; Hee, Charmaine; Ho, Diwei; Taylor, Nicolas L.; Norret, Marck; Smith, Nicole M.; Dunlop, Sarah A.; Iyer, K. Swaminathan; Fitzgerald, Melinda.
In: ACS APPLIED MATERIALS & INTERFACES, Vol. 11, No. 25, 26.06.2019, p. 22085-22095.Research output: Contribution to journal › Article
TY - JOUR
T1 - Elucidating the inability of functionalized nanoparticles to cross the blood-brain barrier and target specific cells in vivo
AU - Naidu, Priya S. R.
AU - Gavriel, Nikolas
AU - Gray, Chloe G. G.
AU - Bartlett, Carole A.
AU - Toomey, Lillian M.
AU - Kretzmann, Jessica A.
AU - Patalwala, Diana
AU - McGonigle, Terence
AU - Denham, Eleanor
AU - Hee, Charmaine
AU - Ho, Diwei
AU - Taylor, Nicolas L.
AU - Norret, Marck
AU - Smith, Nicole M.
AU - Dunlop, Sarah A.
AU - Iyer, K. Swaminathan
AU - Fitzgerald, Melinda
PY - 2019/6/26
Y1 - 2019/6/26
N2 - 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 alpha 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.
AB - 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 alpha 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.
KW - p(HEMA-ran-GMA) nanoparticles
KW - functionalization
KW - protein corona
KW - blood-brain barrier
KW - oligodendrocyte precursor cells
KW - CENTRAL-NERVOUS-SYSTEM
KW - PROTEIN CORONA
KW - SURFACE-CHEMISTRY
KW - PROGENITOR CELLS
KW - DRUG-DELIVERY
KW - INJURY
KW - RAT
KW - TAT
KW - ADSORPTION
KW - PROTEOGLYCAN
U2 - 10.1021/acsami.9b01356
DO - 10.1021/acsami.9b01356
M3 - Article
VL - 11
SP - 22085
EP - 22095
JO - Applied Materials and Interfaces
JF - Applied Materials and Interfaces
SN - 1944-8244
IS - 25
ER -