The End-to-End Molecular Communication Model of Extracellular Vesicle-based Drug Delivery

A closer look at nature has recently brought more interest in exploring and utilizing intra-body communication networks composed of cells as intrinsic, perfectly biocompatible infrastructures to deliver therapeutics. Naturally occurring cell-to-cell communication systems are being manipulated to release, navigate, and take up soluble cell-derived messengers that are either therapeutic by nature or carry therapeutic molecular cargo in their structures. One example of such structures is extracellular vesicles (EVs) which have been recently proven to have favorable pharmacokinetic properties, opening new avenues for developing the next generation biotherapeutics. In this paper, we study theoretical aspects of the EV transfer within heart tissue as a case study by utilizing an information and communication technology-like approach in analyzing molecular communication systems. Our modeling implies the abstraction of the EV releasing cells as transmitters, the extracellular matrix as the channel, and the EV receiving cells as receivers. Our results, derived from the developed analytical models, indicate that the release can be modulated using external forces such as electrical signals, and the transfer and reception can be affected by the extracellular matrix and plasma membrane properties, respectively. The results can predict the EV biodistributions and contribute to avoiding unplanned administration, often resulting in side- and adverse effects.