title: Colloidal Confinement of Polyphosphate on Gold Nanoparticles Robustly Activates the Contact Pathway of Blood Coagulation.
abstract: Platelet-sized polyphosphate (polyP) was functionalized on the surface of gold nanoparticles (GNPs) via a facile conjugation scheme entailing EDAC (N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride)-catalyzed phosphoramidation of the terminal phosphate of polyP to cystamine. Subsequent reduction of the disulfide moiety allowed for anchoring to the colloidal surface. The ability of the synthesized polyP-GNPs to initiate the contact pathway of clotting in human pooled normal plasma (PNP) was then assayed by quantifying changes in viscous, mechanical, and optical properties upon coagulation. It is revealed that the polyP-GNPs are markedly superior contact activators compared to molecularly dissolved, platelet-sized polyP (of equivalent polymer chain length). Moreover, the particles' capacity to mobilize Factor XII (FXII) and its coactivating proteins appear to be identical to very-long-chain polyP typically found in bacteria. These data imply that nanolocalization of anionic procoagulants on colloidal surfaces, achieved through covalent anchoring, may yield a robust contact surface with the ability to sufficiently cluster active clotting factors together above their threshold concentrations to cease bleeding. The polyP-GNPs therefore serve as a promising foundation in the development of a nanoparticle hemostat to treat a range of hemorrhagic scenarios.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Szymusiak
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Donovan
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.forename: Ross
authors.initials: R
authors.lastname: Ransom
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Joseph
authors.initials: J
authors.lastname: Kalkowski
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.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D060326:Chemistry Techniques, Synthetic; D003029:Coagulants / Q000494:pharmacology*; D003102:Colloids / Q000737:chemistry; D003538:Cystamine / Q000737:chemistry; D005174:Factor XII / Q000378:metabolism; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D011122:Polyphosphates / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D003029:Coagulants; D003102:Colloids; D011122:Polyphosphates; D006046:Gold; D005174:Factor XII; D003538:Cystamine