Abstract
Gold nanoparticle (AuNP) physicochemical characteristics, mainly size and charge, modulate their biodistribution, cytotoxicity, and immunorecognition as reported fromin vitroandin vivostudies. While data fromin vitrostudies could be biased by several factors including activation of cells upon isolation and lack of sera proteins in the microenvironment of primary generated cell lines,in vivostudies are costly and time-consuming and require ethics consideration. In this study, we developed a simple and novelin vivo-like method to test for NP immunorecognition from freshly withdrawn human blood samples. AuNPs with a size range of 30 ± 5 nm coated with cationic poly(L-lysine) (PLL) dendrigraft and slightly negative poly(vinyl alcohol) (PVA) were synthesized in water. PLL-capped AuNPs were further coated with poly(ethylene glycol) (PEG) to obtain nearly neutrally charged PEG-AuNPs. Physicochemical properties were determined using zeta potential measurements, UV-Vis spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM). Gel electrophoretic separation, zeta potential, and DLS were also used to characterize our NPs after human blood plasma treatment. PLL-AuNPs showed similar variation in charge and binding affinity to plasma proteins in comparison with PVA-AuNPs. However, PLL-AuNPs.protein complexes revealed a drastic change in size compared to the other tested particles. Results obtained from the neutrophil function test and pyridine formazan extraction revealed the highest activation level of neutrophils (~70%) by 50 μg/mL of PLL-AuNPs compared to a null induction by PEG- and PVA-AuNPs. This observation was further verified by flow cytometry analysis of polymorphonuclear cell size variation in the presence of coated AuNPs. Overall, ourin vivo-like method, to test for NP immunorecognition, proved to be reliable and effective. Finally, our data supports the use of PEG-AuNPs as promising vehicles for drug delivery, as they exhibit minimal protein adsorption affinity and insignificant charge and size variation once introduced in whole blood.
Highlights
In the dawn of a new era of biomedical advancements, nanotechnology has paved the way to manipulate and tailor matters at the nanometer scale, which permits the engineering of a wide array of nanomaterials [1, 2]
Gold nanoparticles were synthesized in water at room temperature through the chemical reduction of gold precursor (HAuCl4.3H2O) with a mid-reducing L-ascorbic acid
In order to avoid uncontrolled increase in the size and to achieve a high stability of the resulting nanoparticles, PLL and poly(vinyl alcohol) (PVA) were added during the synthesis
Summary
In the dawn of a new era of biomedical advancements, nanotechnology has paved the way to manipulate and tailor matters at the nanometer scale, which permits the engineering of a wide array of nanomaterials [1, 2]. Engineered nanoparticles (NPs), gold nanoparticles (AuNPs), are one of the most commonly studied substances due to their widespread use in biomedical applications, cosmetics, and cancer treatment [3,4,5,6,7]. AuNPs exhibit attractive physicochemical and optical properties, fast biodistribution, and dosedependent cytotoxicity [8,9,10,11]. For effective clinical applications, AuNPs should evade the first line of innate immunity mediated by polymorphonuclear cells (PMNs) [12, 13]. NPs must be well designed and properly coated to cross the immune barrier and ensure optimum trafficking to a targeted site with minimal cytotoxicity [14, 15].
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