Targeted Antithrombotic Protein Micelles

Kim, Wookhyun; Haller, Carolyn A.; Dai, Erbin; Wang, Xiaowei; Hagemeyer, Christoph E.; Liu, David Ruchien; Peter, Karlheinz; Chaikof, Elliot L.

doi:10.1002/anie.201408529

Cited by 35 publications

(19 citation statements)

References 46 publications

(60 reference statements)

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“…We have previously demonstrated that the activated GPIIb/IIIa receptor presents suitable neoepitopes for targeting activated platelets, both diagnostically and therapeutically (34,35). The GPIIb/IIIa complex is the most abundant protein expressed on the platelet surface.…”

Section: Discussionmentioning

confidence: 99%

Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis

Hanjaya‐Putra¹,

Haller²,

Wang³

et al. 2018

JCI Insight

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Despite advances in antithrombotic therapy, the risk of recurrent coronary/cerebrovascular ischemia or venous thromboembolism remains high. Dual pathway antithrombotic blockade, using both antiplatelet and anticoagulant therapy, offers the promise of improved thrombotic protection; however, widespread adoption remains tempered by substantial risk of major bleeding. Here, we report a dual pathway therapeutic capable of site-specific targeting to activated platelets and therapeutic enrichment at the site of thrombus growth to allow reduced dosing without compromised antithrombotic efficacy. We engineered a recombinant fusion protein, SCE5-TAP, which consists of a single-chain antibody (SCE5) that targets and blocks the activated GPIIb/IIIa complex, and tick anticoagulant peptide (TAP), a potent direct inhibitor of activated factor X (FXa). SCE5-TAP demonstrated selective platelet targeting and inhibition of thrombosis in murine models of both carotid artery and inferior vena cava thrombosis, without a significant impact on hemostasis. Selective targeting to activated platelets provides an attractive strategy to achieve high antithrombotic efficacy with reduced risk of bleeding complications.

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Section: Discussionmentioning

confidence: 99%

Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis

Hanjaya‐Putra¹,

Haller²,

Wang³

et al. 2018

JCI Insight

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“…Gas-filled microbubbles [93][94][95][96] have densities roughly 1% that of blood [97]. Common biocompatible and the FDA-approved polymeric particles [13,91,98,99], such as poly(lactic acid), poly(glycolic acid), poly(methyl methacrylate), polycaprolactone, and poly (lacticco-glycolic acid), and protein-based nanoparticles tend to have densities either neutrally buoyant or slightly higher than that of blood [100,101]. Liposomes [102,103] are often neutrally buoyant but can have varied densities depending on the density of the medium encapsulated within the liposome [104,105].…”

Section: The Effect Of Particle Densitymentioning

confidence: 99%

The effects of particle size, shape, density and flow characteristics on particle margination to vascular walls in cardiovascular diseases

Truong

Whittaker

et al. 2017

Expert Opinion on Drug Delivery

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Introduction: Vascular-targeted drug delivery is a promising approach for the treatment of atherosclerosis, due to the vast involvement of endothelium in the initiation and growth of plaque, a characteristic of atherosclerosis. One of the major challenges in carrier design for targeting cardiovascular diseases (CVD) is that carriers must be able to navigate the circulation system and efficiently marginate to the endothelium in order to interact with the target receptors. Areas covered: This review draws on studies that have focused on the role of particle size, shape, and density (along with flow hemodynamics and hemorheology) on the localization of the particles to activated endothelial cell surfaces and vascular walls under different flow conditions, especially those relevant to atherosclerosis. Expert opinion: Generally, the size, shape, and density of a particle affect its adhesion to vascular walls synergistically, and these three factors should be considered simultaneously when designing an optimal carrier for targeting CVD. Available preliminary data should encourage more studies to be conducted to investigate the use of nano-constructs, characterized by a sub-micrometer size, a non-spherical shape, and a high material density to maximize vascular wall margination and minimize capillary entrapment, as carriers for targeting CVD. ARTICLE HISTORY

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“…Thus, the development of low‐cost and high‐performance ORR catalysts is in great demand. Since the report on the highly efficient ORR catalyst based on microporous carbon‐supported iron materials, development of non‐precious‐metal ORR catalysts has been a hot research topic …”

Section: Introductionmentioning

confidence: 99%

Facile Synthesis of Fe₃C@Graphene Hybrid Nanorods as an Efficient and Robust Catalyst for Oxygen Reduction Reaction

Wang

Cai

et al. 2016

ChemPlusChem

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Robust and efficient catalysts for the oxygen reduction reaction (ORR) are required for the development of various energy storage and conversion devices. In this study, a durable and high‐performance Fe3C@graphene ORR catalyst has been developed by the carbonization of urea‐ and agar‐modified Fe2O3 nanorods. The influence of the carbonization temperature and annealing time on the activity and stability of the resulting Fe/C catalyst was studied in detail. The Fe/C catalyst synthesized at a temperature of 700 °C (holding time: 60 min) showed better ORR activity and improved stability compared to a commercial Pt/C catalyst. The improved ORR catalytic activity of the catalyst is due to its high Fe3C content and its good durability results from the unique microstructure of the Fe3C@graphene hybrid

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Targeted Antithrombotic Protein Micelles

Cited by 35 publications

References 46 publications

Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis

Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis

The effects of particle size, shape, density and flow characteristics on particle margination to vascular walls in cardiovascular diseases

Facile Synthesis of Fe₃C@Graphene Hybrid Nanorods as an Efficient and Robust Catalyst for Oxygen Reduction Reaction

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Targeted Antithrombotic Protein Micelles

Cited by 35 publications

References 46 publications

Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis

Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis

The effects of particle size, shape, density and flow characteristics on particle margination to vascular walls in cardiovascular diseases

Facile Synthesis of Fe3C@Graphene Hybrid Nanorods as an Efficient and Robust Catalyst for Oxygen Reduction Reaction

Contact Info

Product

Resources

About

Facile Synthesis of Fe₃C@Graphene Hybrid Nanorods as an Efficient and Robust Catalyst for Oxygen Reduction Reaction