Extracellular Vesicle Propagation in Acidic Tumor Microenvironment

A complex and dynamic tumor microenvironment (TME) plays a crucial role in angiogenesis, proliferation, and invasion of tumors. The acidity of the TME has a key impact on the release of extracellular vesicles (EVs) which, in turn, provide novel opportunities to combat tumors. This observation opens up the development of efficient cancer treatment strategies where knowing the EV distribution becomes essential. However, an analytical model of the EV biodistribution which accounts for the effects of extracellular pH (pH(e)) has been missing. Here we propose a simple model for an EV-mediated molecular communications (MC) system which comprises tumor cells as transceivers and the extracellular matrix of the TME as the EV propagating medium. We account for the effect of the acidity considering the pH(e)-modulated EV release from tumor cells, and analytically describe the EV propagation dynamics using a partial differential equation that we solve analytically and verify its solution using the numerical method based on finite element analysis. The obtained results show that the TME acidity characterized with pH values largely affects the EV biodistribution in the TME.