Elucidating the inability of functionalized nanoparticles to cross the blood-brain barrier and target specific cells in vivo

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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)22085-22095
Number of pages11
JournalACS APPLIED MATERIALS & INTERFACES
Volume11
Issue number25
DOIs
Publication statusPublished - 26 Jun 2019

Cite this

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. / Elucidating the inability of functionalized nanoparticles to cross the blood-brain barrier and target specific cells in vivo. In: ACS APPLIED MATERIALS & INTERFACES. 2019 ; Vol. 11, No. 25. pp. 22085-22095.
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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.",
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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 journalArticle

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 -