title: Artificial Dense Granules: A Procoagulant Liposomal Formulation Modeled after Platelet Polyphosphate Storage Pools.
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.
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Donovan
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kalkowski
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Szymusiak
authors.affiliation: Department of Physics, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Canhui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Department of Physics, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Klie
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: James H
authors.initials: JH
authors.lastname: Morrissey
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.|Department of Biopharmaceutical Sciences, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D001777:Blood Coagulation / Q000502:physiology*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism*; D004339:Drug Compounding; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D011122:Polyphosphates / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D008081:Liposomes; D011122:Polyphosphates