The use of quartz crystal microbalance with dissipation (QCM-D) for studying nanoparticle-induced platelet aggregation

Abstract

Abstract:Interactions between blood platelets and nanoparticles have both pharmacological and toxicological significance and may lead to platelet activation and aggregation. Platelet aggregation is usually studied using light aggregometer that neither mimics the conditions found in human microvasculature nor detects microaggregates. A new method for the measurement of platelet microaggregation under flow conditions using a commercially available quartz crystal microbalance with dissipation (QCM-D) has recently been developed. The aim of the current study was to investigate if QCM-D could be used for the measurement of nanoparticle-platelet interactions. Silica, polystyrene, and gold nanoparticles were tested. The interactions were also studied using light aggregometry and flow cytometry, which measured surface abundance of platelet receptors. Platelet activation was imaged using phase contrast and scanning helium ion microscopy. QCM-D was able to measure nanoparticle-induced platelet microaggregation for all nanoparticles tested at concentrations that were undetectable by light aggregometry and flow cytometry. Microaggregates were measured by changes in frequency and dissipation, and the presence of platelets on the sensor surface was confirmed and imaged by phase contrast and scanning helium ion microscopy.

Pharmacological characterization of nanoparticle-induced platelet microaggregation using quartz crystal microbalance with dissipation: comparison with light aggregometry

“…12,13 In addition, we have recently demonstrated that NP-induced platelet aggregation can be detected using QCM-D at NP concentrations that are undetectable by flow cytometry and light transmission aggregometry, both of which are wellestablished methods for measurement of platelet activation and aggregation. 14,15 Although still considered the "gold standard" for testing platelet function, light transmission aggregometry is relatively non-physiological because separated platelets are usually stirred under low shear stress and only form macroaggregates after addition of agonists, ie, conditions that do not accurately mimic platelet adhesion, activation, or aggregation in response to vessel wall damage. 16 The objective of this work was to investigate whether or not this novel approach could also be used to unravel the pharmacology and platelet aggregation pathways that underlie the interactions between NPs and platelets.…”

Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis

“…Upon activation, P-selectin mobilizes to the surface membrane of the activated platelets, is shed from the platelet surface to form sP-selectin, and is released into the bloodstream. [26][27][28][29] The increase of circulation concentration of sP-selectin plays a core role in thrombosis, and inhibition of sP-selectin production has been considered one of the principal mechanisms of antithrombotic agents. Therefore, Figure 3 depicts concentration dependence of AERL inhibiting AA-activated platelets from releasing sP-selectin and discloses a possible mechanism of action of AERL offering in vitro antiplatelet aggregation and in vivo antithrombotic action.…”

Platelets, photosensitizers, and PDT

“…This is the result of attempts to deliver larger amounts of PS selectively to the cell, e.g., in nanoaggregates such as liposomes, to use the enhanced permeability and retention (EPR) effect, which is primarily based on size, or to construct dual modality systems. However, negative effects such as hemolysis, platelet activation and aggregation, generation of reactive nitrogen and oxygen species, leucocyte activation and adhesion and complement activation have been described for nanocarriers aimed at the vascular system [180,181,182,183]. This problem arises from the fact that the nano-targeted vascular system contains large amounts of platelets near the vascular wall and the platelet activating effect of microparticles has been known for almost 50 years [184].…”