Nanoscale effects in dendrimer-mediated targeting of neuroinflammation

Elizabeth Nance, Fan Zhang, Manoj K. Mishra, Zhi Zhang, Siva Pramodh Kambhampati, Kannan Rangaramanujam, Sujatha Kannan

Research output: Contribution to journalArticle

Abstract

Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies.

Original languageEnglish (US)
Pages (from-to)96-107
Number of pages12
JournalBiomaterials
Volume101
DOIs
StatePublished - Sep 1 2016

Fingerprint

Dendrimers
Brain
Neuroglia
Rabbits
Microglia
Biomarkers
Cerebral Palsy
Nervous System Diseases
Blood-Brain Barrier
Astrocytes
Brain Injuries
Chemical activation
Ligands
Phenotype
Imaging techniques
Wounds and Injuries
Pharmaceutical Preparations

Keywords

  • Brain injury
  • Dendrimer
  • Glia
  • Nanoparticle
  • Neuroinflammation

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Nanoscale effects in dendrimer-mediated targeting of neuroinflammation. / Nance, Elizabeth; Zhang, Fan; Mishra, Manoj K.; Zhang, Zhi; Kambhampati, Siva Pramodh; Rangaramanujam, Kannan; Kannan, Sujatha.

In: Biomaterials, Vol. 101, 01.09.2016, p. 96-107.

Research output: Contribution to journalArticle

@article{9c8cfcb64e0048efa3d1eab7659cfb06,
title = "Nanoscale effects in dendrimer-mediated targeting of neuroinflammation",
abstract = "Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies.",
keywords = "Brain injury, Dendrimer, Glia, Nanoparticle, Neuroinflammation",
author = "Elizabeth Nance and Fan Zhang and Mishra, {Manoj K.} and Zhi Zhang and Kambhampati, {Siva Pramodh} and Kannan Rangaramanujam and Sujatha Kannan",
year = "2016",
month = "9",
day = "1",
doi = "10.1016/j.biomaterials.2016.05.044",
language = "English (US)",
volume = "101",
pages = "96--107",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Nanoscale effects in dendrimer-mediated targeting of neuroinflammation

AU - Nance, Elizabeth

AU - Zhang, Fan

AU - Mishra, Manoj K.

AU - Zhang, Zhi

AU - Kambhampati, Siva Pramodh

AU - Rangaramanujam, Kannan

AU - Kannan, Sujatha

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies.

AB - Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies.

KW - Brain injury

KW - Dendrimer

KW - Glia

KW - Nanoparticle

KW - Neuroinflammation

UR - http://www.scopus.com/inward/record.url?scp=84971434999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84971434999&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2016.05.044

DO - 10.1016/j.biomaterials.2016.05.044

M3 - Article

C2 - 27267631

AN - SCOPUS:84971434999

VL - 101

SP - 96

EP - 107

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -