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

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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.

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 - 26 Jun 2019

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10.1021/acsami.9b01356

Naidu et al. 2019 Elucidating the inability
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials and Interfaces, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsami.9b01356
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Targeted nanoparticles to deliver combinations of calcium channel inhibitors to prevent myelin damage during secondary degeneration after neurotrauma
Fitzgerald, M. (Investigator 01), Dunlop, S. (Investigator 02), Swaminatha Iyer, I. (Investigator 03) & Smith, N. (Investigator 04)
NHMRC National Health and Medical Research Council
1/01/15 → 31/12/18
Project: Research
Innovative and multi-disciplinary treatment strategies for secondary degeneration following neurotrauma
Fitzgerald, M. (Investigator 01)
NHMRC National Health and Medical Research Council
1/01/15 → 30/12/18
Project: Research

Cite this

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 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.",

keywords = "p(HEMA-ran-GMA) nanoparticles, functionalization, protein corona, blood-brain barrier, oligodendrocyte precursor cells, CENTRAL-NERVOUS-SYSTEM, PROTEIN CORONA, SURFACE-CHEMISTRY, PROGENITOR CELLS, DRUG-DELIVERY, INJURY, RAT, TAT, ADSORPTION, PROTEOGLYCAN",

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",

year = "2019",

month = jun,

day = "26",

doi = "10.1021/acsami.9b01356",

language = "English",

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pages = "22085--22095",

journal = "ACS APPLIED MATERIALS & INTERFACES",

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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 - 2019/6/26

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.

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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

C2 - 31150197

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

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Targeted nanoparticles to deliver combinations of calcium channel inhibitors to prevent myelin damage during secondary degeneration after neurotrauma

Innovative and multi-disciplinary treatment strategies for secondary degeneration following neurotrauma

Cite this