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

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http://hdl.handle.net/10138/308143

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Balasubramanian , V , Domanskyi , A , Renko , J-M , Sarparanta , M , Wang , C-F , Rebelo Correia , A M , Mäkilä , E , Alanen , O , Salonen , J , Airaksinen , A , Tuominen , R K , Hirvonen , J , Airavaara , M & Santos , H A 2020 , ' Engineered antibody-functionalized porous silicon nanoparticles for therapeutic targeting of pro-survival pathway in endogenous neuroblasts after stroke ' , Biomaterials , vol. 227 , 119556 . https://doi.org/10.1016/j.biomaterials.2019.119556

Title: Engineered antibody-functionalized porous silicon nanoparticles for therapeutic targeting of pro-survival pathway in endogenous neuroblasts after stroke
Author: Balasubramanian, Vimalkumar; Domanskyi, Andrii; Renko, Juho-Matti; Sarparanta, Mirkka; Wang, Chang-Fang; Rebelo Correia, Alexandra Maria; Mäkilä, Ermei; Alanen, Osku; Salonen, Jarno; Airaksinen, Anu; Tuominen, Raimo K.; Hirvonen, Jouni; Airavaara, Mikko; Santos, Hélder A.
Contributor: University of Helsinki, Nanomedicines and Biomedical Engineering
University of Helsinki, Institute of Biotechnology
University of Helsinki, Regenerative pharmacology group
University of Helsinki, Department of Chemistry
University of Helsinki, Nanomedicines and Biomedical Engineering
University of Helsinki, Nanomedicines and Biomedical Engineering
University of Helsinki, Molecular Science
University of Helsinki, Department of Chemistry
University of Helsinki, Regenerative pharmacology group
University of Helsinki, Drug Research Program
University of Helsinki, Neuroscience Center
University of Helsinki, Helsinki One Health (HOH)
Date: 2020-01
Language: eng
Number of pages: 11
Belongs to series: Biomaterials
ISSN: 0142-9612
URI: http://hdl.handle.net/10138/308143
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.
Subject: 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
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