Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain

Neta Zilony-Hanin; Michal Rosenberg; Michal Richman; Ronen Yehuda; Hadas Schori; Menachem Motiei; Shai Rahimipour; Alexander Groisman; Ester Segal; Orit Shefi

doi:10.1002/smll.201904203

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain

Neta Zilony-Hanin, Michal Rosenberg, Michal Richman, Ronen Yehuda, Hadas Schori, Menachem Motiei, Shai Rahimipour, Alexander Groisman, Ester Segal, Orit Shefi

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

31 Scopus citations

Abstract

Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO₂) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aβ)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO₂ chips above the dura mater, and biolistic bombardment of PSiO₂ microparticles through an opening in the skull using a pneumatic gene gun. The PSiO₂-implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO₂ carriers as potential localized delivery systems for NGF to the brain.

Original language	English
Article number	1904203
Journal	Small
Volume	15
Issue number	45
DOIs	https://doi.org/10.1002/smll.201904203
State	Published - 1 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Funding

N.Z.-H. and M.R. contributed equally to this work. E.S. and M.R. acknowledge the financial support of the Russell Berrie Nanotechnology Institute at the Technion. The authors thank Dr. Nitzan Dahan from the Life Sciences and Engineering Infrastructure Center at the Technion for his valuable support in using the light-sheet fluorescence microscope. The assistance of Lee Friedman in establishing the quantification protocol of NGF release is acknowledged. The authors also thank Omer Sabach and Dr. Noa Alon for their valuable contribution to the graphical illustrations.

Funders	Funder number
Life Sciences and Engineering Infrastructure Center
Russell Berrie Nanotechnology Institute
Technion-Israel Institute of Technology

Keywords

Alzheimer's disease
biolistics
brain
delivery
nerve growth factor
porous silicon

Access to Document

10.1002/smll.201904203

Cite this

@article{12de4e51698e4600871a3f9cabb039c7,

title = "Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain",

abstract = "Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO2) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aβ)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO2 chips above the dura mater, and biolistic bombardment of PSiO2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO2-implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO2 carriers as potential localized delivery systems for NGF to the brain.",

keywords = "Alzheimer's disease, biolistics, brain, delivery, nerve growth factor, porous silicon",

author = "Neta Zilony-Hanin and Michal Rosenberg and Michal Richman and Ronen Yehuda and Hadas Schori and Menachem Motiei and Shai Rahimipour and Alexander Groisman and Ester Segal and Orit Shefi",

note = "Publisher Copyright: {\textcopyright} 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2019",

month = nov,

day = "1",

doi = "10.1002/smll.201904203",

language = "אנגלית",

volume = "15",

journal = "Small",

issn = "1613-6810",

publisher = "Wiley-VCH Verlag",

number = "45",

}

TY - JOUR

T1 - Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain

AU - Zilony-Hanin, Neta

AU - Rosenberg, Michal

AU - Richman, Michal

AU - Yehuda, Ronen

AU - Schori, Hadas

AU - Motiei, Menachem

AU - Rahimipour, Shai

AU - Groisman, Alexander

AU - Segal, Ester

AU - Shefi, Orit

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO2) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aβ)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO2 chips above the dura mater, and biolistic bombardment of PSiO2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO2-implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO2 carriers as potential localized delivery systems for NGF to the brain.

AB - Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO2) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aβ)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO2 chips above the dura mater, and biolistic bombardment of PSiO2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO2-implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO2 carriers as potential localized delivery systems for NGF to the brain.

KW - Alzheimer's disease

KW - biolistics

KW - brain

KW - delivery

KW - nerve growth factor

KW - porous silicon

UR - http://www.scopus.com/inward/record.url?scp=85071762308&partnerID=8YFLogxK

U2 - 10.1002/smll.201904203

DO - 10.1002/smll.201904203

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 31482695

SN - 1613-6810

VL - 15

JO - Small

JF - Small

IS - 45

M1 - 1904203

ER -

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this