Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection

Bapurao Surnar, Uttara Basu, Bhabatosh Banik, Anis Ahmad, Brian Marples, Nagesh Kolishetti, Shanta Dhar

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The success of nanoparticle-mediated delivery of antioxidant and antiinflammatory-based neuroprotectants to the brain to improve neuronal functions in neurodegenerative diseases has demonstrated lesser impact instead of achieving its full potential. We hypothesized that these failures were due to a combination of parameters, such as: (i) unavailability of a delivery vehicle, which can reproducibly and efficiently transport through the brain capillary endothelium; (ii) inefficient uptake of therapeutic nanoparticles in the neuronal cell population; and (iii) limited ability of a single nanoparticle to cross the two most-impermeable biological barriers, the blood–brain barrier and mitochondrial double membrane, so that a nanoparticle can travel through the brain endothelial barrier to the mitochondria of target cells where oxidative damage is localized. Herein, we demonstrate optimization of a biodegradable nanoparticle for efficient brain accumulation and protection of astrocytes from oxidative damage and mitochondrial dysfunctions to enhance the neuroprotection ability of astrocytes toward neurons using neurodegeneration characteristics in SOD1G93A rats. This biodegradable nanomedicine platform with the ability to accumulate in the brain has the potential to bring beneficial effects in neurodegenerative diseases by modulating the stars, astrocytes in the brain, to enhance their neuroprotective actions.

Original languageEnglish (US)
Pages (from-to)E12333-E12342
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number52
DOIs
StatePublished - Dec 26 2018

Fingerprint

Nanotechnology
Nanoparticles
Membranes
Brain
Astrocytes
Neurodegenerative Diseases
Nanomedicine
Vascular Endothelium
Mitochondrial Membranes
Neuroprotective Agents
Neuroprotection
Mitochondria
Anti-Inflammatory Agents
Antioxidants
Neurons
Population

Keywords

  • Astrocyte injury
  • Blood–brain barrier
  • Inflammation
  • Mitochondria

ASJC Scopus subject areas

  • General

Cite this

Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection. / Surnar, Bapurao; Basu, Uttara; Banik, Bhabatosh; Ahmad, Anis; Marples, Brian; Kolishetti, Nagesh; Dhar, Shanta.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 52, 26.12.2018, p. E12333-E12342.

Research output: Contribution to journalArticle

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