Abstract

Generation of new neurons by utilizing the regenerative potential of adult neural stem cells (NSCs) and neuroblasts is an emerging therapeutic strategy to treat various neurodegenerative diseases, including neuronal loss after stroke. Committed to neuronal lineages, neuroblasts are differentiated from NSCs and have a lower proliferation rate. In stroke the proliferation of the neuroblasts in the neurogenic areas is increased, but the limiting factor for regeneration is the poor survival of migrating neuroblasts. Survival of neuroblasts can be promoted by small molecules; however, new drug delivery methods are needed to specifically target these cells. Herein, to achieve specific targeting, we have engineered biofunctionalized porous silicon nanoparticles (PSi NPs) conjugated with a specific antibody against polysialylated neural cell adhesion molecule (PSA-NCAM). The PSi NPs loaded with a small molecule drug, SC-79, were able to increase the activity of the Akt signaling pathway in doublecortin positive neuroblasts both in cultured cells and in vivo in the rat brain. This study opens up new possibilities to target drug effects to migrating neuroblasts and facilitate differentiation, maturation and survival of developing neurons. The conjugated PSi NPs are a novel tool for future studies to develop new therapeutic strategies aiming at regenerating functional neurocircuitry after stoke.
Original languageEnglish
Article number119556
JournalBiomaterials
Volume227
Number of pages11
ISSN0142-9612
DOIs
Publication statusPublished - Jan 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • Akt pathway activation
  • Antibody bioconjugation
  • BIOCOMPATIBILITY
  • BRAIN
  • DIFFERENTIATION
  • DRUG-DELIVERY
  • IN-VITRO
  • NANOMEDICINE
  • NEURAL STEM-CELLS
  • NEUROGENESIS
  • Neuron regeneration
  • Porous silicon nanoparticles
  • SMALL-MOLECULE
  • SURFACE-CHEMISTRY
  • Targeting neuroblasts
  • 317 Pharmacy
  • 3112 Neurosciences

Cite this

@article{effcacb10e274be68e8073d2ccdd84e6,
title = "Engineered antibody-functionalized porous silicon nanoparticles for therapeutic targeting of pro-survival pathway in endogenous neuroblasts after stroke",
abstract = "Generation of new neurons by utilizing the regenerative potential of adult neural stem cells (NSCs) and neuroblasts is an emerging therapeutic strategy to treat various neurodegenerative diseases, including neuronal loss after stroke. Committed to neuronal lineages, neuroblasts are differentiated from NSCs and have a lower proliferation rate. In stroke the proliferation of the neuroblasts in the neurogenic areas is increased, but the limiting factor for regeneration is the poor survival of migrating neuroblasts. Survival of neuroblasts can be promoted by small molecules; however, new drug delivery methods are needed to specifically target these cells. Herein, to achieve specific targeting, we have engineered biofunctionalized porous silicon nanoparticles (PSi NPs) conjugated with a specific antibody against polysialylated neural cell adhesion molecule (PSA-NCAM). The PSi NPs loaded with a small molecule drug, SC-79, were able to increase the activity of the Akt signaling pathway in doublecortin positive neuroblasts both in cultured cells and in vivo in the rat brain. This study opens up new possibilities to target drug effects to migrating neuroblasts and facilitate differentiation, maturation and survival of developing neurons. The conjugated PSi NPs are a novel tool for future studies to develop new therapeutic strategies aiming at regenerating functional neurocircuitry after stoke.",
keywords = "Akt pathway activation, Antibody bioconjugation, BIOCOMPATIBILITY, BRAIN, DIFFERENTIATION, DRUG-DELIVERY, IN-VITRO, NANOMEDICINE, NEURAL STEM-CELLS, NEUROGENESIS, Neuron regeneration, Porous silicon nanoparticles, SMALL-MOLECULE, SURFACE-CHEMISTRY, Targeting neuroblasts, 317 Pharmacy, 3112 Neurosciences",
author = "Vimalkumar Balasubramanian and Andrii Domanskyi and Juho-Matti Renko and Mirkka Sarparanta and Chang-Fang Wang and {Rebelo Correia}, {Alexandra Maria} and Ermei M{\"a}kil{\"a} and Osku Alanen and Jarno Salonen and Anu Airaksinen and Tuominen, {Raimo K.} and Jouni Hirvonen and Mikko Airavaara and Santos, {H{\'e}lder A.}",
year = "2020",
month = "1",
doi = "10.1016/j.biomaterials.2019.119556",
language = "English",
volume = "227",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "ELSEVIER SCI IRELAND LTD",

}

TY - JOUR

T1 - Engineered antibody-functionalized porous silicon nanoparticles for therapeutic targeting of pro-survival pathway in endogenous neuroblasts after stroke

AU - Balasubramanian, Vimalkumar

AU - Domanskyi, Andrii

AU - Renko, Juho-Matti

AU - Sarparanta, Mirkka

AU - Wang, Chang-Fang

AU - Rebelo Correia, Alexandra Maria

AU - Mäkilä, Ermei

AU - Alanen, Osku

AU - Salonen, Jarno

AU - Airaksinen, Anu

AU - Tuominen, Raimo K.

AU - Hirvonen, Jouni

AU - Airavaara, Mikko

AU - Santos, Hélder A.

PY - 2020/1

Y1 - 2020/1

N2 - Generation of new neurons by utilizing the regenerative potential of adult neural stem cells (NSCs) and neuroblasts is an emerging therapeutic strategy to treat various neurodegenerative diseases, including neuronal loss after stroke. Committed to neuronal lineages, neuroblasts are differentiated from NSCs and have a lower proliferation rate. In stroke the proliferation of the neuroblasts in the neurogenic areas is increased, but the limiting factor for regeneration is the poor survival of migrating neuroblasts. Survival of neuroblasts can be promoted by small molecules; however, new drug delivery methods are needed to specifically target these cells. Herein, to achieve specific targeting, we have engineered biofunctionalized porous silicon nanoparticles (PSi NPs) conjugated with a specific antibody against polysialylated neural cell adhesion molecule (PSA-NCAM). The PSi NPs loaded with a small molecule drug, SC-79, were able to increase the activity of the Akt signaling pathway in doublecortin positive neuroblasts both in cultured cells and in vivo in the rat brain. This study opens up new possibilities to target drug effects to migrating neuroblasts and facilitate differentiation, maturation and survival of developing neurons. The conjugated PSi NPs are a novel tool for future studies to develop new therapeutic strategies aiming at regenerating functional neurocircuitry after stoke.

AB - Generation of new neurons by utilizing the regenerative potential of adult neural stem cells (NSCs) and neuroblasts is an emerging therapeutic strategy to treat various neurodegenerative diseases, including neuronal loss after stroke. Committed to neuronal lineages, neuroblasts are differentiated from NSCs and have a lower proliferation rate. In stroke the proliferation of the neuroblasts in the neurogenic areas is increased, but the limiting factor for regeneration is the poor survival of migrating neuroblasts. Survival of neuroblasts can be promoted by small molecules; however, new drug delivery methods are needed to specifically target these cells. Herein, to achieve specific targeting, we have engineered biofunctionalized porous silicon nanoparticles (PSi NPs) conjugated with a specific antibody against polysialylated neural cell adhesion molecule (PSA-NCAM). The PSi NPs loaded with a small molecule drug, SC-79, were able to increase the activity of the Akt signaling pathway in doublecortin positive neuroblasts both in cultured cells and in vivo in the rat brain. This study opens up new possibilities to target drug effects to migrating neuroblasts and facilitate differentiation, maturation and survival of developing neurons. The conjugated PSi NPs are a novel tool for future studies to develop new therapeutic strategies aiming at regenerating functional neurocircuitry after stoke.

KW - Akt pathway activation

KW - Antibody bioconjugation

KW - BIOCOMPATIBILITY

KW - BRAIN

KW - DIFFERENTIATION

KW - DRUG-DELIVERY

KW - IN-VITRO

KW - NANOMEDICINE

KW - NEURAL STEM-CELLS

KW - NEUROGENESIS

KW - Neuron regeneration

KW - Porous silicon nanoparticles

KW - SMALL-MOLECULE

KW - SURFACE-CHEMISTRY

KW - Targeting neuroblasts

KW - 317 Pharmacy

KW - 3112 Neurosciences

U2 - 10.1016/j.biomaterials.2019.119556

DO - 10.1016/j.biomaterials.2019.119556

M3 - Article

VL - 227

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

M1 - 119556

ER -