Beyond the thrombus: Platelet-inspired nanomedicine approaches in inflammation, immune response, and cancer.

The traditional role of platelets is in the formation of blood clots for physiologic (e.g., in hemostasis) or pathologic (e.g., in thrombosis) functions. The cellular and subcellular mechanisms and signaling in platelets involved in these functions have been extensively elucidated and new knowledge continues to emerge, resulting in various therapeutic developments in this area for the management of hemorrhagic or thrombotic events. Nanomedicine, a field involving design of nanoparticles with unique biointeractive surface modifications and payload encapsulation for disease-targeted drug delivery, has become an important component of such therapeutic development. Beyond their traditional role in blood clotting, platelets have been implicated to play crucial mechanistic roles in other diseases including inflammation, immune response, and cancer, via direct cellular interactions, as well as secretion of soluble factors that aid in the disease microenvironment. To date, the development of nanomedicine systems that leverage these broader roles of platelets has been limited. Additionally, another exciting area of research that has emerged in recent years is that of platelet-derived extracellular vesicles (PEVs) that can directly and indirectly influence physiological and pathological processes. This makes PEVs a unique paradigm for platelet-inspired therapeutic design. This review aims to provide mechanistic insight into the involvement of platelets and PEVs beyond hemostasis and thrombosis, and to discuss the current state of the art in the development of platelet-inspired therapeutic technologies in these areas, with an emphasis on future opportunities.