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

doi:10.1021/acsami.9b01356

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

Drug Delivery Disposition & Dynamics

Research output: Contribution to journal › Article › Research › peer-review

21 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	22085–22095
Number of pages	11
Journal	ACS Applied Materials & Interfaces
Volume	11
Issue number	25
DOIs	https://doi.org/10.1021/acsami.9b01356
Publication status	Published - 31 May 2019

Keywords

blood-brain barrier
functionalization
oligodendrocyte precursor cells
p(HEMA- ran-GMA) nanoparticles
protein corona

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsami.9b01356

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Naidu, P. S. R., Gavriel, N., Gray, C. G. G., Bartlett, C. A., Toomey, L. M., Kretzmann, J. A., Patalwala, D., McGonigle, T., Denham, E., Hee, C., Ho, D., Taylor, N. L., Norret, M., Smith, N. M., Dunlop, S. A., Iyer, K. S., & Fitzgerald, M. (2019). Elucidating the Inability of Functionalized Nanoparticles to Cross the Blood-Brain Barrier and Target Specific Cells in Vivo. ACS Applied Materials & Interfaces, 11(25), 22085–22095. https://doi.org/10.1021/acsami.9b01356

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title = "Elucidating the Inability of Functionalized Nanoparticles to Cross the Blood-Brain Barrier and Target Specific Cells in Vivo",

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 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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author = "Naidu, {Priya S.R.} and Nikolas Gavriel and Gray, {Chloe G.G.} and Bartlett, {Carole A.} and Toomey, {Lillian M.} and Kretzmann, {Jessica A.} and Diana Patalwala and Terence McGonigle and Eleanor Denham and Charmaine Hee and Diwei Ho and Taylor, {Nicolas L.} and Marck Norret and Smith, {Nicole M.} and Dunlop, {Sarah A.} and Iyer, {K. Swaminathan} and Melinda Fitzgerald",

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doi = "10.1021/acsami.9b01356",

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Naidu, PSR, Gavriel, N, Gray, CGG, Bartlett, CA, Toomey, LM, Kretzmann, JA, Patalwala, D, McGonigle, T, Denham, E, Hee, C, Ho, D, Taylor, NL, Norret, M, Smith, NM, Dunlop, SA, Iyer, KS & Fitzgerald, M 2019, 'Elucidating the Inability of Functionalized Nanoparticles to Cross the Blood-Brain Barrier and Target Specific Cells in Vivo', ACS Applied Materials & Interfaces, vol. 11, no. 25, pp. 22085–22095. https://doi.org/10.1021/acsami.9b01356

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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 - 2019/5/31

Y1 - 2019/5/31

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 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.

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 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.

KW - blood-brain barrier

KW - functionalization

KW - oligodendrocyte precursor cells

KW - p(HEMA- ran-GMA) nanoparticles

KW - protein corona

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DO - 10.1021/acsami.9b01356

M3 - Article

C2 - 31150197

AN - SCOPUS:85068005743

SN - 1944-8244

VL - 11

SP - 22085

EP - 22095

JO - ACS Applied Materials & Interfaces

JF - ACS Applied Materials & Interfaces

IS - 25

ER -

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

Abstract

Keywords

UN SDGs

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