Platelet Mimetic Particles for Targeting Thrombi in Flowing Blood

Doshi, Nishit; Orje, Jennifer N.; Molins, Blanca; Smith, Jeffrey W.; Mitragotri, Samir; Ruggeri, Zaverio M.

doi:10.1002/adma.201200607

Cited by 105 publications

(102 citation statements)

References 30 publications

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“…Rod-shaped particles prepared from these materials will enhance the specificity of tissue-specific targets. Various tissue-specific targets have been identified for targeting various diseases, including anti-ICAM-1 and anti-platelet endothelial cell adhesion molecule (PECAM) antibodies for inflamed endothelium (61), synthetic peptides such as RGD for tumor neovasculature (62,63), and von Willebrand factor or platelet glycoprotein for damaged vessels or activated platelets (64). The specificity of these targeting ligands may be enhanced further by placing them on shape-engineered nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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590

507

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Vascular endothelium offers a variety of therapeutic targets for the treatment of cancer, cardiovascular diseases, inflammation, and oxidative stress. Significant research has been focused on developing agents to target the endothelium in diseased tissues. This includes identification of antibodies against adhesion molecules and neovascular expression markers or peptides discovered using phage display. Such targeting molecules also have been used to deliver nanoparticles to the endothelium of the diseased tissue. Here we report, based on in vitro and in vivo studies, that the specificity of endothelial targeting can be enhanced further by engineering the shape of ligand-displaying nanoparticles. In vitro studies performed using microfluidic systems that mimic the vasculature (synthetic microvascular networks) showed that rodshaped nanoparticles exhibit higher specific and lower nonspecific accumulation under flow at the target compared with their spherical counterparts. Mathematical modeling of particle-surface interactions suggests that the higher avidity and specificity of nanorods originate from the balance of polyvalent interactions that favor adhesion and entropic losses as well as shear-induced detachment that reduce binding. In vivo experiments in mice confirmed that shape-induced enhancement of vascular targeting is also observed under physiological conditions in lungs and brain for nanoparticles displaying anti-intracellular adhesion molecule 1 and anti-transferrin receptor antibodies.biodistribution | morphology | SMN | cylinder | drug delivery

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Section: Discussionmentioning

confidence: 99%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

590

507

View full text Add to dashboard Cite

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“…8 The A1 domain of the secreted VWF interacts with GPIba, a ligand-binding protein within the glycoprotein GP-Ib-V-IX complex on the platelet's surface, allowing the platelets to adhere to the damaged vascular wall. [9][10][11] GPIba also allows platelets to activate under high-shear conditions, which facilitates platelet aggregation at wound sites. 10 The activated platelets then spread along the wall and adhere to each other, forming a platelet plug to stem initial blood loss.…”

Section: Platelets In Coagulation and Hemostasismentioning

confidence: 99%

“…11,36,38 Doshi et al 11 formed synthetic plateletlike particles by stretching polymeric particles into a discoid shape reminiscent of the true shape of natural platelets, crosslinking alternating layers of bovine serum albumin and polyelectrolytes over the stretched discoid particles, then degrading the polymeric core to leave a flexible discoid capable of imitating the mechanical stretching of natural platelets. 11 Anselmo et al 36 also made use of a layer-by-layer synthesis method with a degraded core to imitate innate platelet deformability while synthesizing their own platelet-like nanoparticles (Figure 2).…”

Section: Artificial Plateletsmentioning

confidence: 99%

“…11 Anselmo et al 36 also made use of a layer-by-layer synthesis method with a degraded core to imitate innate platelet deformability while synthesizing their own platelet-like nanoparticles (Figure 2). 36 In an alternative approach, Brown et al 38,53 used soft pNIPAM-based microgels synthesized via precipitation polymerization to yield ultra-low cross-linked particles with a high degree of flexibility that allow for extensive spreading within fibrin clots.…”

Section: Artificial Plateletsmentioning

confidence: 99%

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Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

Nandi

Brown

2016

Exp Biol Med (Maywood)

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Platelets closely interface with the immune system to fight pathogens, target wound sites, and regulate tissue repair. Natural platelet levels within the body can be depleted for a variety of reasons, including excessive bleeding following traumatic injury, or diseases such as cancer and bacterial or viral infections. Platelet transfusions are commonly used to improve platelet count and hemostatic function in these cases, but transfusions can be complicated by the contamination risks and short storage life of donated platelets. Lyophilized platelets that can be freeze-dried and stored for longer periods of time and synthetic plateletmimetic technologies that can enhance or replace the functions of natural platelets, while minimizing adverse immune responses have been explored as alternatives to transfusion. Synthetic platelets typically comprise nanoparticles surface-decorated with peptides or ligands to recreate specific biological characteristics of platelets, including targeting of wound and disease sites and facilitating platelet aggregation. Recent efforts in synthetic platelet design have additionally focused on matching platelet shape and mechanics to recreate the marginalization and clot contraction capabilities of natural platelets. The ability to specifically tune the properties of synthetic platelet-mimetic materials has shown utility in a variety of applications including hemostasis, drug delivery, and targeted delivery of cancer therapeutics.

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“…Polystyrene microparticles were stretched to form biconvex discoidal shape and then tailored with recombinant platelet glycoprotein vWF-A1 (Doshi et al 2012). The artificial platelets were intended for drug delivery and shown to mimic the adhesion mechanism of natural platelets upon shear stress stimulation.…”

Section: Synthetic Material-based Productionmentioning

confidence: 99%

Recent developments in ex vivo platelet production

2016

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The platelet is a component of blood that functions to initiate blood clotting. Abnormal platelet count and function can lead to a life-threatening condition caused by excessive bleeding. At present, platelet supply for transfusion can be obtained only from platelet donation. However, platelets cannot be stored for longer than 7 days, meaning that routine isolation is required to maintain platelet supply for transfusion. To mitigate for potential platelet shortages, several strategies have been proposed to generate platelets ex vivo. By employing both of natural and artificial approaches, several researchers have successfully generated biomaterials with characteristics similar to human-derived platelets. Their reports indicated that the biomaterials could mimic the aggregation of human-isolated platelets, further suggesting the possibility to substitute or complement human-isolated platelets. The current review summarizes the progress in ex vivo platelet production and gives a prospect for the possible approaches to achieving a feasible platelet factory, based on the Good Manufacturing Practice standards.

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Platelet Mimetic Particles for Targeting Thrombi in Flowing Blood

Cited by 105 publications

References 30 publications

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

Recent developments in ex vivo platelet production

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