Fig. 8

Therapeutic concept and mode of action of the “Trojan horse” treatment using PLT and PEV as a drug delivery system. PC is collected from patients or donors then centrifuged at 1500 xg for 10 min to pelletize PLT. PLT is incubated with a DOX solution in PAS for 1 h to generate DOX-loaded PLT. DOX-loaded PLT is frozen in the presence of 6% DMSO following approved procedures and stored at − 80 °C until use. After thawing, a therapeutic dose of cryopreserved DOX-loaded PLT is transfused to the patient. Through the blood circulation, the cryopreserved DOX-loaded PLT reaches the tumour micro-environment where cancer cells release pro-coagulant factors and EV involving TF-EV. TF-EV convert prothrombin in blood to thrombin resulting in PLT activation. Cryopreserved DOX-loaded PLT activation in the tumour microenvironment contributes to the release of DOX and of PEV-DOX that induce cancer cell death. The figure of tumour with blood vessel was prepared using Servier Medical Art (www.servier.com). Abbreviations: PLT: platelet, PEV: PLT-derived extracellular vesicle, PC: PLT concentrate, PAS: PLT additive solution, DMSO: dimethyl sulfoxide, TF-EV: EV expressing tissue factor