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Biomacromolecules. 2016 Aug 8;17(8):2572-81. doi: 10.1021/acs.biomac.6b00577. Epub 2016 Jul 27.

Artificial Dense Granules: A Procoagulant Liposomal Formulation Modeled after Platelet Polyphosphate Storage Pools.

Author information

1
Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
2
Department of Physics, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
3
Department of Biochemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
4
Department of Biopharmaceutical Sciences, University of Illinois at Chicago , Chicago, Illinois 60607, United States.

Abstract

Granular platelet-sized polyphosphate nanoparticles (polyP NPs) were encapsulated in sterically stabilized liposomes, forming a potential, targeted procoagulant nanotherapy resembling human platelet dense granules in both structure and functionality. Dynamic light scattering (DLS) measurements reveal that artificial dense granules (ADGs) are colloidally stable and that the granular polyP NPs are encapsulated at high efficiencies. High-resolution scanning transmission electron microscopy (HR-STEM) indicates that the ADGs are monodisperse particles with a 150 nm diameter dense core consisting of P, Ca, and O surrounded by a corrugated 25 nm thick shell containing P, C, and O. Further, the ADGs manifest promising procoagulant activity: Detergent solubilization by Tween 20 or digestion of the lipid envelope by phospholipase C (PLC) allows for ADGs to trigger autoactivation of Factor XII (FXII), the first proteolytic step in the activation of the contact pathway of clotting. Moreover, ADGs' ability to reduce the clotting time of human plasma in the presence of PLC further demonstrate the feasibility to develop ADGs into a potential procoagulant nanomedicine.

PMID:
27405511
DOI:
10.1021/acs.biomac.6b00577
[Indexed for MEDLINE]

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