Using PEG-PLGA-PLL nanoparticles to mimic platelets

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Researchers have synthesized a nanoparticle that replicates the function of a platelet to assist in the body’s defense against major blood loss after injuries. The body’s conventional defense when injury occurs involves collagen exposure, glycoprotein interaction, the activation of integrins on the platelets, and the expression of an enzyme. When collagen is detected by a platelet, glycoproteins bind strongly to the collagen, holding them in place at the site of the wound. The activated integrins anchor platelets to the extracellular matrix, while the expressed enzyme promotes the formation of a fibrin net over the platelet plug to stop bleeding[2]. The nanoparticle researchers have created acts as an artificial platelet that is injected near a wound to amplify the clotting process when the body’s normal supply of platelets is insufficient. The nanoparticles mimic the shape, flexibility, and surface chemistry of a natural platelet. Amino acid functionalities on surface glycoproteins with a specific affinity for collagen allow the nanoparticles to anchor directly to exposed collagen. This helps form the initial platelet plug. The artificial platelets also have an affinity only for activated platelets, and won’t cause inactivated platelets to activate, as over-activation that could cause thrombosis and stroke. To achieve these properties, platelet cores of polylactic-co-glycolic acid-poly-L-lysine (PLGA-PLL) and polyethylene glycol (PEG) arms were selected, with Arg-Gly-Asp (RGD) functionalities attached at the end of the arms to control platelet interactions as glycoproteins would. The combination of these polymers were studied and proven the most desirable nanoparticles for use in these artificial platelets. Alternatives were tested by varying the PEG arm length and by using variations of the RGD functionality, all of which displayed a decrease in adhesion and aggregation when observed in an in vitro assay[3]. Moving forward, the developers of this product hope to see it gain viability for use in on-site trauma treatment and ubiquitous clinical application. 

References

  1. Bertram JP, Williams CA, Robinson R, Segal SS, Flynn NT, Lavik EB. Intravenous Hemostat: Nanotechnology to Halt Bleeding. Science Translational Medicine [Internet]. 2009 ;1(11):11ra22 - 11ra22. Available from: http://stm.sciencemag.org/cgi/doi/10.1126/scitranslmed.3000397
  2. Anselmo AC, Modery-Pawlowski CLynn, Menegatti S, Kumar S, Vogus DR, Tian LL, Chen M, Squires TM, Gupta ASen, Mitragotri S. Platelet-like Nanoparticles: Mimicking Shape, Flexibility, and Surface Biology of Platelets To Target Vascular Injuries. ACS Nano [Internet]. 2014 ;8(11):11243 - 11253. Available from: http://pubs.acs.org/doi/abs/10.1021/nn503732mhttp://pubs.acs.org/doi/pdf/10.1021/nn503732m
  3. Citekey <span>10.1126/scitranslmed.3000397 not found

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Synthetic nanoparticle platelets are capable of addressing internal injuries that could not otherwise be treated with existing technology, which mainly relies on external application. The synthetic platelets have been clinically proven to assist coagulation efficiently enough to cut bleeding time in half. Additionally, excess nanoparticles that do no stick to the wound site are metabolized after 1-2 days and removed from the bloodstream. This method has proven more effective than the currently used injectable treatment, recombinant factor VIIa. The synthetic nanoparticles have potential for application in battlefield injuries where timely medical treatment may not be available[1].

References

  1. Brown AC, Stabenfeldt SE, Ahn B, Hannan RT, Dhada KS, Herman ES, Stefanelli V, Guzzetta N, Alexeev A, Lam WA, et al. Ultrasoft microgels displaying emergent platelet-like behaviours. Nature Materials [Internet]. 2014 ;13(12):1108 - 1114. Available from: http://www.nature.com/doifinder/10.1038/nmat4066

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The polymers used in this technology, PLGA-PLL and PEG, are already in widespread use in medical devices and pharmaceutical industries. It is believed that the proven safety records of these polymers in these fields will translate to a successful clinical application. The platelet is designed to bind uniquely to fibrin, which reduces the risk of unwanted clotting at sites other than the wound. The platelet injection process, however, has so far been tested in a rat model only. Risk for human application is currently undetermined.

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