Abstract
Presentation Description :
Extracellular vesicles (EVs) are membrane bound nano-sized vesicles containing diverse bioactive cargo. The molecular content of small EVs/exosomes reflects their cell of origin, which makes them ideal source of non-invasive liquid biopsy for tumors like Retinoblastoma (RB), where tissue biopsy is contraindicated due to the risk of extraocular spread. EVs exhibit low immunogenicity and low cytotoxicity. Thus, they could be used as attractive biological vesicles for the efficient delivery of therapeutics across different biological barriers to target cells. In this context, different research groups have focused on RB derived EVs to elucidate their role in tumor progression, as a source for identifying diagnostic and prognostic biomarkers, therapeutic targets and also as drug delivery vehicles. In vitro and in vivo murine xenotransplantation model showed that RB-derived small EVs prompted tumor progression by infiltrating the microenvironment via their miRNA cargo, C-X-C chemokine receptor type 4 and thrombospondin-1. They could also promote angiogenesis of human vesicle endothelial cells through microRNA 92a 3p. RB vitreous seeding primary cell line-derived small EV proteins are shown to be involved in extracellular matrix remodeling and interaction. The proliferative capacity of RB cells can be inhibited by exosome mediated transfer of miR-142-3p from monocytes. Comprehensive analysis of RB-serum small EVs revealed the regulatory role of miRNAs and lncRNAs in cell cycle and metabolism. In addition, a recent study highlighted the enhanced efficacy of Doxorubicin-loaded EVs against RB cells. While the prospects seem promising, the challenges are also well identified.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.