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

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.

The emerging role of breast cancer derived extracellular vesicles-mediated intercellular communication in ovarian cancer progression and metastasis.

Breast cancer is one of the most occurring cancer types in women worldwide and metastasizes to several organs such as bone, lungs, liver, brain, and ovaries. Extracellular vesicles (EVs) mediate intercellular signaling which has a profound effect on tumor development and metastasis. Recent developments in the field of EVs provide an opportunity to investigate the roles of EVs released from tumor cells in metastasis. In this study, we compared the effects of metastatic breast cancer-derived EVs on both nonluteinized granulosa HGrC1 and ovarian cancer OVCAR-3 cells in terms of proliferation, invasion, apoptosis, and gene expression levels. EVs were isolated from the culture medium of metastatic breast cancer cell line MDA-MB-231 by ultracentrifugation. Cell proliferation, apoptosis, cell cycle, invasion, and cellular uptake analysis were performed to clarify the roles of tumor-derived EVs in both cells. 6.85 × 108 nanoparticles of BCD-EVs were markedly increased cell proliferation as well as invasion capacity. Exposing the cells with BCD-EVs for 24 h, resulted in an accumulation of both cells in G2/M phase as determined by flow cytometry. The apoptosis assay results were consistent with cell proliferation and cell cycle results. The uptake of the BCD-EVs was efficiently internalized by both cells. In addition, marked variations in fatty acid composition between cells were observed. BCD-EVs appeared new fatty acids in HGrC1. Besides, BCD-EVs upregulated epithelial-mesenchymal transition (EMT) and proliferation-related genes. In conclusion, an environment of tumor-derived EVs changes the cellular phenotype of cancer and noncancerous cells and may lead to tumor progression and metastasis.