A1 Refereed original research article in a scientific journal
Engineered antibody-functionalized porous silicon nanoparticles for therapeutic targeting of pro-survival pathway in endogenous neuroblasts after stroke
Authors: Vimalkumar Balasubramanian, Andrii Domanskyi, Juho-Matti Renko, Mirkka Sarparanta, Chang-Fang Wang, Alexandra Correia, Ermei Mäkilä, Osku S. Alanen, Jarno Salonen, Anu J. Airaksinen, Raimo Tuominen, Jouni Hirvonen, Mikko Airavaara, Hélder A. Santos
Publisher: ELSEVIER SCI LTD
Publication year: 2020
Journal: Biomaterials
Journal name in source: BIOMATERIALS
Journal acronym: BIOMATERIALS
Article number: UNSP 119556
Volume: 227
Number of pages: 11
ISSN: 0142-9612
eISSN: 1878-5905
DOI: https://doi.org/10.1016/j.biomaterials.2019.119556
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/43822366
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.
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