Cytosolic perfluorocarbon delivery to platelets via albumin for antithrombotic therapy.

Thrombosis is a major contributor to global disease burden. Antiplatelet therapy is the critical approach to prevent thrombosis by reducing platelet reactivity. However, classical antiplatelet strategies generally interfere with platelet integrin α IIb β 3 -mediated platelet activation, thereby facing severe bleeding risk. To break the limitation, we described an integrin α IIb β 3 -independent antiplatelet method by cytosolic delivery of nanoscale perfluorocarbon (PFC) to platelets via albumin carrier. Denatured albumin was found to build high affinity with platelets to mediate cytosolic PFC delivery. While, cytosolic PFC impaired cytoskeleton reorganization during platelet activation to inhibit relevant platelet functions, but avoided to interfere with integrin α IIb β 3. We proved that this α IIb β 3 -indenpendent antiplatelet pattern showed potential antiplatelet effect with low bleeding risk to prevent thrombosis in various thrombosis models. Together, cytosolic PFC delivery via albumin is a promising antiplatelet approach, and will provide an alternative regimen for current antithrombotic therapy. [Display omitted] • Perfluorocarbon combined with albumin produced potential antiplatelet effect. • Albumin-mediated cytosolic perfluorocarbon delivery to platelets inhibited cytoskeleton-dependent platelets functions. • Different from classical antiplatelet agents, this is an integrin α IIb β 3 -independent antiplatelet pattern. • Intravenous injection of PFC@Ab nanoparticles improved antithrombotic therapy with low bleeding risk. [ABSTRACT FROM AUTHOR]