Platelet‐inspired nanomedicine in hemostasis thrombosis and thromboinflammation

Abstract

Platelets are anucleate cell‐fragments derived predominantly from megakaryocytes in the bone marrow and released in the blood circulation, with a normal count of 150 000–40 000 per μl and a lifespan of approximately 10 days in humans. A primary role of platelets is to aid in vascular injury site‐specific clot formation to stanch bleeding, termed hemostasis. Platelets render hemostasis by a complex concert of mechanisms involving platelet adhesion, activation and aggregation, coagulation amplification, and clot retraction. Additionally, platelet secretome can influence coagulation kinetics and clot morphology. Therefore, platelet defects and dysfunctions result in bleeding complications. Current treatment for such complications involve prophylactic or emergency transfusion of platelets. However, platelet transfusion logistics constantly suffer from limited donor availability, challenges in portability and storage, high bacterial contamination risks, and very short shelf life (~5 days). To address these issues, an exciting area of research is focusing on the development of microparticle‐ and nanoparticle‐based platelet surrogate technologies that can mimic various hemostatic mechanisms of platelets. On the other hand, aberrant occurrence of the platelet mechanisms lead to the pathological manifestation of thrombosis and thromboinflammation. The treatments for this are focused on inhibiting the mechanisms or resolving the formed clots. Here, platelet‐inspired technologies can provide unique platforms for disease‐targeted drug delivery to achieve high therapeutic efficacy while avoiding systemic side‐effects. This review will provide brief mechanistic insight into the role of platelets in hemostasis, thrombosis and thromboinflammation, and present the current state‐of‐art in the design of platelet‐inspired nanomedicine for applications in these areas.

Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents

“…The heteromultivalent modification strategy taking advantage of more combinatorial platelet activation processes (including adhesion, aggregation, thrombin amplification, secretion, and clot retraction) has become a critical principle in hemostats development, especially the phosphatidylserine exposure process. 42 PLT-PFC only retained platelet surface proteins with limited phosphatidylserine exposure, thus the prohemostatic effect was negligible. On the contrary, PLT-PFC may act as a sink for ligands including adenosine diphosphate and fibrinogen especially in antiplatelet drug-free blood, which may counteract its prohemostatic potential.…”

“…Existing platelet-inspired technologies mainly focus on reducing contamination risks and increasing platelet shelf-life in vivo and storage in vitro. 42 …”

“…Hopefully, further comprehensive insights into the role of platelets will facilitate the development of platelet-inspired nanomedicine applied in more clinical scenarios. 42 Overall, our strategy holds great promise for prophylactically and therapeutically improving the clinical benefits of antiplatelet therapy.…”

Complement component C1q initiates extrinsic coagulation via the receptor for the globular head of C1q in adventitial fibroblasts and vascular smooth muscle cells

“…This can lead to severe reductions in blood flow to downstream tissue or a complete blockage of blood flow from the heart 3 . Conventionally, atherosclerosis has been considered vascular in nature; however, it has recently become apparent that atherosclerosis can be characterized by changes in both the thrombotic and inflammatory responses and that these changes can have wide‐ranging systemic effects 4,5 …”

“…3 Conventionally, atherosclerosis has been considered vascular in nature; however, it has recently become apparent that atherosclerosis can be characterized by changes in both the thrombotic and inflammatory responses and that these changes can have wideranging systemic effects. 4,5 The result of physiological or pathological coagulation can cause blood vessels to become obstructed through the formation of a thrombus. The intrinsic and extrinsic coagulation cascades can each result in thrombus formation; however, it is the extrinsic cascade that has more physiological relevance.…”