A Perspective on the Characterization of Early Neural Progenitor Cell-Derived Extracellular Vesicles for Targeted Delivery to Neuroblastoma Cells

• Published in: Neurochemical research 2024-09, Vol.49 (9), p.2364-2378
• Main Authors: Kırbaş, Oğuz Kaan, Bozkurt, Batuhan Turhan, Yıldırım, Melis Rahime, Taşlı, Pakize Neslihan, Abdik, Hüseyin, Şahin, Fikrettin, Avşar Abdik, Ezgi
• Format: Article
• Language: English
• Subjects: Bioaccumulation; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blood circulation; Blood-brain barrier; Cell Biology; Cell differentiation; Cell Differentiation - physiology; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; Cells (biology); Doublecortin protein; Drug carriers; Drug delivery; Drug Delivery Systems - methods; Extracellular vesicles; Extracellular Vesicles - metabolism; Fibroblasts - metabolism; Gene transfer; Humans; Immune response; Immunosuppressive agents; Neonates; Nestin; Neural stem cells; Neural Stem Cells - metabolism; Neuroblastoma; Neuroblasts; Neurochemistry; Neurology; Neurosciences; Original Paper; Progenitor cells; Signalling systems; SOXB1 Transcription Factors; Vesicles
• ISSN: 0364-3190; 1573-6903; 1573-6903
• DOI: 10.1007/s11064-024-04165-1

As an element of the cellular signaling systems, extracellular vesicles (EVs) exhibit many desirable traits for usage as targeted delivery vehicles. When administered, EVs cause little to no toxic or immune response, stay in circulation for longer periods compared to synthetic carriers, preferentially accumulate in tissues that are the same or similar to their cell-of-origin and can pass through the blood-brain barrier. Combined, these traits make neural EVs a particularly promising tool for delivering drugs to the brain. This study aims to combine tissue and EVs engineering to prepare neural differentiated cells derived EVs that exhibit neural properties, to develop an effective, tissue-homing drug and gene delivery platform for the brain. Early neural differentiated cell-derived EVs were produced with neural characteristics from neural differentiated human neonatal dermal fibroblasts. The EVs carried key neural proteins such as Nestin, Sox2 and Doublecortin. The cellular uptake of early neural differentiated cell-derived EVs was higher compared to non-neural EVs during in vitro uptake assays on neuroblastoma cells. Moreover, eND-EVs were significantly decreased the viability of neuroblastoma cells. In conclusion, this study revealed that early neural differentiated cell-derived EVs have potential as a promising drug carrier for the treatment of various neural disorders. Graphical Abstract