Colloidal Confinement of Polyphosphate on Gold Nanoparticles Robustly Activates the Contact Pathway of Blood Coagulation
| Autor: | Alexander J. Donovan, Ying Liu, Magdalena Szymusiak, Ross Ransom, Stephanie A. Smith, Hao Shen, James H. Morrissey, Joseph Kalkowski |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Hydrochloride Cystamine Biomedical Engineering Metal Nanoparticles Pharmaceutical Science Bioengineering Nanotechnology Chemistry Techniques Synthetic Article 03 medical and health sciences Colloid chemistry.chemical_compound Polyphosphates otorhinolaryngologic diseases Humans Moiety Coagulation (water treatment) Colloids Blood Coagulation Pharmacology Factor XII Coagulants Chemistry Polyphosphate Organic Chemistry digestive system diseases 030104 developmental biology Colloidal gold Biophysics Gold Biotechnology |
| Zdroj: | Bioconjug Chem |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.5b00524 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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