Combination targeting of ‘platelets + fibrin’ enhances clot anchorage efficiency of nanoparticles for vascular drug delivery

Abstract

Occlusive thrombosis is a central pathological event in heart attack, stroke, thromboembolism etc. Therefore, pharmacological thrombolysis or anticoagulation is used in treating these diseases. However, systemic administration of such drugs...

Platelet‐inspired nanomedicine in hemostasis thrombosis and thromboinflammation

“…121 In yet another heteromultivalent approach, liposomes were surface-decorated with a combination of GPIIb-IIIa-binding and fibrin-binding peptides, and this design maximized the clot-localization of the nanoparticles under shear flow. 122 The Poly-NIPAM based low-crosslinked fibrinbinding gel particles stated previously (see Section 2) have also recently been shown to deliver tPA for fibrin-targeted treatment of disseminated intravascular coagulation. 123 In thromboinflammatory pathologies, current treatments predoiminantly use systemic (e.g.…”

“…In further advancement of this approach, our work has focused on co‐decorating drug‐loaded liposomes with a combination of active platelet GPIIb‐IIIa‐binding and P‐selectin‐binding peptides, to enhance the clot‐targeting capability and therapeutic effect of the particles 121 . In yet another heteromultivalent approach, liposomes were surface‐decorated with a combination of GPIIb‐IIIa‐binding and fibrin‐binding peptides, and this design maximized the clot‐localization of the nanoparticles under shear flow 122 . The Poly‐NIPAM based low‐crosslinked fibrin‐binding gel particles stated previously (see Section 2) have also recently been shown to deliver tPA for fibrin‐targeted treatment of disseminated intravascular coagulation 123 …”

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

“…This suggests that platelet‐mimetic synthetic nanoparticles could be potentially used for targeting transplant sites to deliver anti‐inflammatory and immunosuppressant drugs as well as molecular imaging agents to improve localized therapeutic and diagnostic efficacy while avoiding systemic risks. In our research focused on the development of platelet‐inspired nanomedicine, we have demonstrated the ability to mimic various platelet interactions (e.g., adhesion to VWF and collagen, aggregation mediated by fibrinogen, binding mediated by P‐selectin, anchorage to fibrin, heterotypic binding to activated neutrophils) via decoration of liposomal nanoparticle platforms with combinations of biointeractive peptides 11,72,73 . We envision that such surface‐engineered nanoparticle platforms could be potentially customized for targeted delivery of appropriate therapeutic agents in the management of immune and inflammatory pathologies.…”

“…In our research focused on the development of platelet-inspired nanomedicine, we have demonstrated the ability to mimic various platelet interactions (e.g., adhesion to VWF and collagen, aggregation mediated by fibrinogen, binding mediated by P-selectin, anchorage to fibrin, heterotypic binding to activated neutrophils) via decoration of liposomal nanoparticle platforms with combinations of biointeractive peptides. 11,72,73 We envision that such surface-engineered nanoparticle platforms could be potentially customized for targeted delivery of appropriate therapeutic agents in the management of immune and inflammatory pathologies.…”

Nanomedicines for hemorrhage control

“…Incorporating a combination of ligands on the surfaces of nanoparticles increases their adhesion to sites of injury. 28 Lipid-based nanoparticles are commonly used in drug delivery and in many approved drugs. Liposomes loaded with tranexamic acid and targeted to sites of bleeding significantly reduced blood loss and improved survival after rat liver hemorrhage.…”