Anne-Laure Papa and colleagues have created decoys of platelets - the body's clot-forming blood cells - that prevented the formation of dangerous blood clots in vessels (or thrombosis) and combated cancer metastasis in preclinical models. Their decoys - whose effects can be reversed far faster compared to standard antiplatelet drugs - represent a promising therapeutic strategy for treating thrombosis and cancer metastasis, two leading causes of death and disability worldwide. Platelets play a vital role in the human circulatory system, as they protect the body from bleeding and maintain the integrity of blood vessels. However, hyperactive platelets also contribute to an array of diseases - patients with thrombosis often have elevated platelet counts, which can also promote the spread of malignant cancer cells. Currently available antiplatelet drugs can inhibit platelet activation, but reversal of the effects they exert requires at least one week, making them risky for patients who have suffered a trauma or other life-threatening situations. To overcome this obstacle, Papa et al. created a rapidly reversible antiplatelet therapy inspired by platelet "decoys." The decoys did not aggregate and became activated in the same manner as normal platelets but maintained their ability to interact with other cells. They also inhibited harmful adhesion and aggregation of functional platelets and reduced the severity of thrombosis in a rabbit model. Importantly their effects were immediately reversed with an injection of fresh, functional platelets. They also displayed wide-ranging anticancer effects - the decoys broke up platelet-mediated aggregation of human breast cancer cells, prevented their spread in a chip model of the human vasculature, and inhibited metastatic tumor growth in mice. The fast reversibility of the therapy indicates it could one day prevent life-threatening bleeding in clinical emergencies or surgical settings, the authors say.
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Journal
Science Translational Medicine