Non-Enzymatic Remodeling of Fibrin Biopolymers via Photothermally Triggered Radical-Generating Nanoparticles

• Published in: Chemistry of materials Vol. 26; no. 17; pp. 5120 - 5130
• Main Authors: Walker, Joan M, Zaleski, Jeffrey M
• Format: Journal Article
• Language: English
• Published: American Chemical Society 09-09-2014
• ISSN: 0897-4756; 1520-5002
• DOI: 10.1021/cm5024713

Thrombosis is a hallmark of several chronic diseases leading to potentially fatal heart attacks and strokes. Frontline interventions include intravenous delivery of potent, enzymatic fibrinolytics that possess a high risk for inducing systemic bleeding. As a conceptual countermeasure, we have developed a water-soluble PEGylated gold nanoparticle appended with the enediyne diamine (Z)-octa-4-en-2,6-diyne-1,8-diamine that is capable of photothermally generating 1,4-diradical species under visible excitation (λ = 514 nm, 100 mW, 2–6 h). In the absence of biopolymer substrate, photothermal excitation of these particles leads to self-quenching polymer coating formation in water. When these radical-generating nanoparticles are intrinsically applied toward the blood clot structural protein assembly fibrin, as well as its nonpolymerized precursor protein fibrinogen, scanning electron microscopy images reveal significantly modified fibrin clot morphology, as evidenced by larger void spaces and collapsed fiber regions. Quantitatively, laser confocal microscopy images of Alexa Fluor 488-labeled fibrin clots extrinsically treated with nanoparticles at the clot/solution interface show that photothermal radical formation by these particles leads to marked increase in the number of larger pore sizes (>2.0 μm) within the fibrin matrix, which derive from a corresponding decrease in the histogram of smaller pore sizes (1.5–2.0 μm). These larger pore sizes ultimately result in total perfusion of solution through the entire clot volume. The chemical manifestation of this is that radical-induced modifications occur mainly at the protein level but lead to morphological changes at the micron scale. Overall, this technology could have significant impact for disease states such as deep vein thrombosis via a localized, catheter-delivered approach.