An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake

Gerard H. Bode; Gregory Coue; Christian Freese; Karin E. Pickl; Maria Sanchez-Purra; Berta Albaiges; Salvador Borros; Ewoud C. van Winden; Leto-Aikaterini Tziveleka; Zili Sideratou; Johan F. J. Engbersen; Smriti Singh; Krystyna Albrecht; Juergen Groll; Martin Moeller; Andy J. G. Poetgens; Christoph Schmitzk; Eleonore Froehlich; Christian Grandfils; Frank M. Sinner; C. James Kirkpatrick; Harry W. M. Steinbusch; Hans-Georg Frank; Ronald E. Unger; Pilar Martinez-Martinez

doi:10.1016/j.nano.2016.11.009

An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake

Gerard H. Bode, Gregory Coue, Christian Freese, Karin E. Pickl, Maria Sanchez-Purra, Berta Albaiges, Salvador Borros, Ewoud C. van Winden, Leto-Aikaterini Tziveleka, Zili Sideratou, Johan F. J. Engbersen, Smriti Singh, Krystyna Albrecht, Juergen Groll, Martin Moeller, Andy J. G. Poetgens, Christoph Schmitzk, Eleonore Froehlich, Christian Grandfils, Frank M. SinnerC. James Kirkpatrick, Harry W. M. Steinbusch, Hans-Georg Frank, Ronald E. Unger, Pilar Martinez-Martinez^*

^*Corresponding author for this work

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

13 Citations (Web of Science)

Abstract

Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. (C) 2016 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	1289-1300
Number of pages	12
Journal	Nanomedicine-Nanotechnology Biology and Medicine
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.nano.2016.11.009
Publication status	Published - Apr 2017

Keywords

Nanoparticles
Peptides
Brain
Targeting
80-COATED POLYBUTYLCYANOACRYLATE NANOPARTICLES
DRUG-DELIVERY
SENSITIVE HYDROGELS
MEDIATED TRANSPORT
DENDRITIC POLYMERS
NANOGELS
CELLS
DENDRIMERS
LIPOSOMES
METHOTREXATE

Access to Document

10.1016/j.nano.2016.11.009

Cite this

Bode, G. H., Coue, G., Freese, C., Pickl, K. E., Sanchez-Purra, M., Albaiges, B., Borros, S., van Winden, E. C., Tziveleka, L-A., Sideratou, Z., Engbersen, J. F. J., Singh, S., Albrecht, K., Groll, J., Moeller, M., Poetgens, A. J. G., Schmitzk, C., Froehlich, E., Grandfils, C., ... Martinez-Martinez, P. (2017). An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake. Nanomedicine-Nanotechnology Biology and Medicine, 13(3), 1289-1300. https://doi.org/10.1016/j.nano.2016.11.009

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title = "An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake",

abstract = "Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. (C) 2016 Elsevier Inc. All rights reserved.",

keywords = "Nanoparticles, Peptides, Brain, Targeting, 80-COATED POLYBUTYLCYANOACRYLATE NANOPARTICLES, DRUG-DELIVERY, SENSITIVE HYDROGELS, MEDIATED TRANSPORT, DENDRITIC POLYMERS, NANOGELS, CELLS, DENDRIMERS, LIPOSOMES, METHOTREXATE",

author = "Bode, {Gerard H.} and Gregory Coue and Christian Freese and Pickl, {Karin E.} and Maria Sanchez-Purra and Berta Albaiges and Salvador Borros and {van Winden}, {Ewoud C.} and Leto-Aikaterini Tziveleka and Zili Sideratou and Engbersen, {Johan F. J.} and Smriti Singh and Krystyna Albrecht and Juergen Groll and Martin Moeller and Poetgens, {Andy J. G.} and Christoph Schmitzk and Eleonore Froehlich and Christian Grandfils and Sinner, {Frank M.} and Kirkpatrick, {C. James} and Steinbusch, {Harry W. M.} and Hans-Georg Frank and Unger, {Ronald E.} and Pilar Martinez-Martinez",

year = "2017",

month = apr,

doi = "10.1016/j.nano.2016.11.009",

language = "English",

volume = "13",

pages = "1289--1300",

journal = "Nanomedicine-Nanotechnology Biology and Medicine",

issn = "1549-9634",

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Bode, GH, Coue, G, Freese, C, Pickl, KE, Sanchez-Purra, M, Albaiges, B, Borros, S, van Winden, EC, Tziveleka, L-A, Sideratou, Z, Engbersen, JFJ, Singh, S, Albrecht, K, Groll, J, Moeller, M, Poetgens, AJG, Schmitzk, C, Froehlich, E, Grandfils, C, Sinner, FM, Kirkpatrick, CJ, Steinbusch, HWM, Frank, H-G, Unger, RE & Martinez-Martinez, P 2017, 'An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake', Nanomedicine-Nanotechnology Biology and Medicine, vol. 13, no. 3, pp. 1289-1300. https://doi.org/10.1016/j.nano.2016.11.009

An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting : The importance of selective blood-brain barrier uptake. / Bode, Gerard H.; Coue, Gregory; Freese, Christian et al.

In: Nanomedicine-Nanotechnology Biology and Medicine, Vol. 13, No. 3, 04.2017, p. 1289-1300.

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

TY - JOUR

T1 - An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting

T2 - The importance of selective blood-brain barrier uptake

AU - Bode, Gerard H.

AU - Coue, Gregory

AU - Freese, Christian

AU - Pickl, Karin E.

AU - Sanchez-Purra, Maria

AU - Albaiges, Berta

AU - Borros, Salvador

AU - van Winden, Ewoud C.

AU - Tziveleka, Leto-Aikaterini

AU - Sideratou, Zili

AU - Engbersen, Johan F. J.

AU - Singh, Smriti

AU - Albrecht, Krystyna

AU - Groll, Juergen

AU - Moeller, Martin

AU - Poetgens, Andy J. G.

AU - Schmitzk, Christoph

AU - Froehlich, Eleonore

AU - Grandfils, Christian

AU - Sinner, Frank M.

AU - Kirkpatrick, C. James

AU - Steinbusch, Harry W. M.

AU - Frank, Hans-Georg

AU - Unger, Ronald E.

AU - Martinez-Martinez, Pilar

PY - 2017/4

Y1 - 2017/4

N2 - Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. (C) 2016 Elsevier Inc. All rights reserved.

AB - Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. (C) 2016 Elsevier Inc. All rights reserved.

KW - Nanoparticles

KW - Peptides

KW - Brain

KW - Targeting

KW - 80-COATED POLYBUTYLCYANOACRYLATE NANOPARTICLES

KW - DRUG-DELIVERY

KW - SENSITIVE HYDROGELS

KW - MEDIATED TRANSPORT

KW - DENDRITIC POLYMERS

KW - NANOGELS

KW - CELLS

KW - DENDRIMERS

KW - LIPOSOMES

KW - METHOTREXATE

U2 - 10.1016/j.nano.2016.11.009

DO - 10.1016/j.nano.2016.11.009

M3 - Article

C2 - 27884636

SN - 1549-9634

VL - 13

SP - 1289

EP - 1300

JO - Nanomedicine-Nanotechnology Biology and Medicine

JF - Nanomedicine-Nanotechnology Biology and Medicine

IS - 3

ER -