Dosing extracellular vesicles.

Extracellular vesicles (EVs) are natural nanoparticles containing biologically active molecules. They are important mediators of intercellular communication and can be exploited therapeutically by various bioengineering approaches. To accurately determine the therapeutic potential of EVs in pre-clinical and clinical settings, dependable dosing strategies are of utmost importance. However, the field suffers from inconsistencies comprising all areas of EV production and characterisation. Therefore, a standardised and well-defined process in EV quantification, key to reliable therapeutic EV dosing, remains to be established. Here, we examined 64 pre-clinical studies for EV-based therapeutics with respect to their applied EV dosing strategies. We identified variations in effective dosing strategies irrespective of the applied EV purification method and cell source. Moreover, we found dose discrepancies depending on the disease model, where EV doses were selected without accounting for published EV pharmacokinetics or biodistribution patterns. We therefore propose to focus on qualitative aspects when dosing EV-based therapeutics, such as the potency of the therapeutic cargo entity. This will ensure batch-to-batch reliability and enhance reproducibility between applications. Furthermore, it will allow for the successful benchmarking of EV-based therapeutics compared to other nanoparticle drug delivery systems, such as viral vector-based or lipid-based nanoparticle approaches.

Selenofolate inhibits the proliferation of IGROV1 cancer cells independently from folate receptor alpha.

Cancer is one of the main causes of human mortality worldwide and novel chemotherapeutics are required due to the limitations of conventional cancer therapies. For example, using redox selenium compounds as novel chemotherapeutics seem to be very promising. The objective of this study was to explore if folate could be used as a carrier to deliver a newly synthesised selenium derivative selenofolate into cancer cells. Particularly, the cytotoxic effects of this selenofolate compound were investigated in a variety of cancer cell types including lung, liver, and cervical cancers and specifically IGROV1 cells. Our results showed that selenofolate inhibits the growth of cancer cells in-vitro. However, despite the expectations, folate receptor alpha (FRα) was not involved in the transportation of selenofolate compound into the cells i.e. growth inhibition was independent of FRα, suggesting that multiple transporters (e.g. reduced folate carrier-1) are possibly involved in the delivery and internalisation of folate in IGROV1 cells. Additionally, selenofolate did not exert cell death through apoptosis. Instead, anti-proliferative activity showed to be the main cause of growth inhibition of selenolofate in the IGROV1 cell line. In conclusion, selenofolate inhibits the growth of cancer cells and thus, may be explored further as a potential chemotherapeutic agent.