Abstract
Zinc oxide nanoparticles (ZnO NPs) have many biomedical applications such as chemotherapy agents, vaccine adjuvants, and biosensors but its hemocompatibility is still poorly understood, especially in the event of direct contact of NPs with blood components. Here, we investigated the impact of size and surface functional groups on the platelet homeostasis. ZnO NPs were synthesized in two different sizes (20 and 100 nm) and with three different functional surface groups (pristine, citrate, and L-serine). ZnO NPs were incubated with plasma collected from healthy rats to evaluate the coagulation time, kinetics of thrombin generation, and profile of levels of coagulation factors in the supernatant and coronated onto the ZnO NPs. Measurements of plasma coagulation time showed that all types of ZnO NPs prolonged both active partial thromboplastin time and prothrombin time in a dose-dependent manner but there was no size- or surface functionalization-specific pattern. The kinetics data of thrombin generation showed that ZnO NPs reduced the thrombin generation potential with functionalization-specificity in the order of pristine > citrate > L-serine but there was no size-specificity. The profile of levels of coagulation factors in the supernatant and coronated onto the ZnO NPs after incubation of platelet-poor plasma with ZnO NPs showed that ZnO NPs reduced the levels of coagulation factors in the supernatant with functionalization-specificity. Interestingly, the pattern of coagulation factors in the supernatant was consistent with the levels of coagulation factors adsorbed onto the NPs, which might imply that ZnO NPs simply adsorb coagulation factors rather than stimulating these factors. The reduced levels of coagulation factors in the supernatant were consistent with the delayed coagulation time and reduced potential for thrombin generation, which imply that the adsorbed coagulation factors are not functional.
Highlights
The rapid increase in the need and usage of nanomaterials in various fields may necessarily increase human exposure to these materials, but the potential hazards and interactions with biological systems are still poorly understood [1, 2]
The pristine 20 nm-sized Zinc oxide nanoparticles (ZnO NPs) were purchased from Sumitomo Osaka Cement Co, Ltd. (Lot#: 141319; Tokyo, Japan) and 100 nm-sized ZnO NPs were obtained from American Elements (Lot#: 1871511079–673; Los Angeles, CA, USA)
scanning electron microscopy (SEM) images showed that all types of ZnO NPs were spherically shaped with a narrow size distribution range (Fig 1)
Summary
The rapid increase in the need and usage of nanomaterials in various fields may necessarily increase human exposure to these materials, but the potential hazards and interactions with biological systems are still poorly understood [1, 2]. Nanomaterials have been applied in biomedical applications such as drug delivery vehicles, therapeutic agents, biosensors, and laboratory diagnostics and zinc oxide nanoparticles (ZnO NP) are one of the leading candidates for these applications [3]. Spherical ZnO NPs are the most popular type, which can be used for various applications including as anti-cancer and anti-bacterial agents, and one of the main mechanisms for these applications is production of reactive oxygen species (ROS) and induction of apoptosis [4,5,6]. Composite types of nanostructures are synthesized in various forms including ZnO quantum dots and ZnO nanoclusters for the purpose of anti-cancer activity as well as anti-bacterial agents [11,12,13]. Because of the various applications and advantages of ZnO NPs, the Organization for Economic Cooperation and Development (OECD) initiative adopted ZnO NP as one of 13 nanomaterials for evaluation [14]
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