In vivoandIn vitroToxicity and Anti-Inflammatory Properties of Gold Nanoparticle Bioconjugates to the Vascular System

Abstract

Gold nanoparticle (AuNP) bioconjugates have been used as therapeutic and diagnostic tools; however, in vivo biocompatibility and cytotoxicity continue to be two fundamental issues. The effect of AuNPs (20 nm) conjugated with antibody [immunoglobulin G (IgG)], albumin, protein A, PEG4000, and citrate (cit) were evaluated in vitro using primary human cells of the vascular system. AuNP bioconjugates did not cause lysis of human erythrocytes, apoptosis or necrosis of human leukocytes, and endothelial cells in vitro, although AuNPs had been internalized and detected in the cytoplasm. Moreover, the influence of AuNPs on rheological parameters, blood and vessel wall characteristics was investigated in vivo by intravital microscopy assay using male Wistar rats mesentery microcirculation as model. Intravenous injection of AuNP-IgG or cit-AuNP did not cause hemorrhage, hemolysis or thrombus formation, instead suppressed the leukocyte adhesion to postcapillary vessel walls, an early stage of an inflammatory process. Furthermore, AuNP-IgG abrogated the expression of platelet-endothelial cell adhesion molecule-1, chemotaxis, and oxidative burst activation on neutrophils after leukotriene B4 stimulation, a membrane receptor-dependent stimulus, thus confirming their anti-inflammatory effects in vitro. The expression of oxidative burst activation was also suppressed after stimulating AuNP-IgG-treated neutrophils with lipid-soluble phorbol myristate acetate (PMA), confirming the direct intracellular action of AuNP-IgG on the inflammatory process in vitro. Our in vitro and in vivo experimental approaches highlighted the great potentiality of AuNP bioconjugates for therapeutic and diagnostic applications by parenteral routes.

A multi-target therapeutic potential of Prunus domestica gum stabilized nanoparticles exhibited prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory and analgesic properties.

“…Current management of inflammatory processes can be improved by the use of biodegradable nanoplatforms that specifically deliver anti-inflammatory molecules to inflamed tissues [50]. Nanobiomaterials based on gold nanoparticles conjugated with biomolecules possessed unique anti-inflammatory properties by reducing the leukocyte-endothelium interaction and leukocyte influx to adjacent tissues after leukotriene B4 stimulation in vivo as well as producing a marked reduction of chemotaxis and oxidative burst activation in vitro [51]. …”

The curious case of how mimicking physiological complexity in in vitro models of the human respiratory system influences the inflammatory responses. A preliminary study focused on gold nanoparticles

“…Inhaled AuNPs are in fact often associated with inflammation inhibition (Jacobsen et al, ), as well as with poor translocation from the lung to distant organs (Sung et al, ), making them perfect candidates as drug carrier for lung diseases treatment. A significant AuNPs‐induced down‐regulation of the inflammatory signals has also been detected in other organs and cell models (Chen et al, ; Khan, Abdelhalim, Alhomida, & Al‐Ayed, M. S., ; Selim, Abd‐Elhakim, & Al‐Ayadhi, ; Sumbayev et al, ; Uchiyama et al, ; Villiers, Freitas, Couderc, Villiers, & Marche, ). This could potentially open novel therapeutic options for the use of AuNPs as anti‐inflammatory agents.…”

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

“…14 In fact, many efforts have been carried out to evaluate the biocompatibility and possible adverse effects of SPIOs. For example, Wu et al 15 determined the biodistribution, clearance, and biocompatibility of oleic acid-Pluronic layer coated SPIOs (core diameter of 11 nm).…”