Modeling gold nanoparticle biodistribution after arterial infusion into perfused tissue: effects of surface coating, size and protein corona

Abstract

A detailed understanding of the factors governing nanomaterial biodistribution is needed to rationally design safe nanomedicines. This research details the pharmacokinetics of gold nanoparticle (AuNP) biodistribution after arterial infusion of 40 or 80 nm AuNP (1 μg/ml) into the isolated perfused porcine skin flap (IPPSF). AuNP had surface coatings consisting of neutral polyethylene glycol (PEG), anionic lipoic acid (LA), or cationic branched polyethylenimine (BPEI). Effect of a porcine plasma corona (PPC) on 40 nm BPEI and PEG-AuNP were assessed in the IPPSF. Au concentrations were determined by ICP/MS and arterial to venous concentration-time profiles were analyzed over 8 hr (4 hr infusion, 4 hr washout) using a two-compartment pharmacokinetic model. IPPSF viability and vascular function were assessed by change in glucose utilization, vascular resistance, or weight gain after perfusion. All AuNP demonstrated some degree of AuNP arterial extraction and skin flap retention, as well as enhanced kinetic parameters of tissue uptake; with BPEI-AuNP consistently having the greatest biodistribution even with a PPC. Toxicological effects were not detected. Transmission electron microscopy confirmed intracellular uptake of AuNP. These studies paralleled previous in vitro cell culture studies using the same AuNP in human endothelial and renal proximal tubule cells, hepatocytes, keratinocytes, showing BPEI-AuNP having the greatest uptake, although the presence of a PPC did not reduce IPPSF biodistribution as in the cell culture studies. These findings clearly indicate arterial to the venous extraction of AuNP after infusion with the magnitude of extraction being greatest with the BPEI surface coating and provide data and model structure necessary to construct the whole body physiologically based pharmacokinetic models capable of utilizing available in vitro data.

Advances in Gold Nanoparticle-Based Combined Cancer Therapy

“…As a result, smaller GNPs can contribute to an inflammatory response, due to their interactions with these proteins, highlighting the necessity for proper functionalization [91]. Another factor that impacts biodistribution is the surface charge, which can be controlled by various surface conjugations, such as with PEG [92,93]. The addition of PEG to 20 nm glucose-functionalized GNPs has been shown to increase the half-life period from 1.23 h to 6.17 h [94].…”

Boosting nanotoxicity to combat multidrug-resistant bacteria in pathophysiological environments

“…Biomolecule coronas may transform NMs by also modulating their colloidal stability and/or zeta potential. 4,10,11,22,29,35,[38][39][40]44,45,47,48,54,55,65 Summarizing the results of numerous studies, (patho)biological and ecological environments seem to be facing mainly negatively-charged, protein corona-covered NMs, irrespective of the NM's initial zeta potential. 46,55,59,[66][67][68] Although we only tested a selection of relevant NMs, our data demonstrates that binding to also negatively charged bacteria occurs and thus, that binding cannot be predicted by colloidal electrostatics alone in the absence or presence of biomolecules.…”

Quantifying the relative contribution of particulate versus dissolved silver to toxicity and uptake kinetics of silver nanowires in lettuce: impact of size and coating

“…From those papers, morphological comparison studies of nanomaterials showed that the dissolution behavior and the biological effects of wire-shaped nanomaterials are distinctly different from the dissolution behavior and adverse effects of nanosphere or nanoplate analogues (M€ uller et al 2010;George et al 2012;Sohn et al 2015;Nam and An 2019). Intrinsic properties such as size, surface chemistry, and charge of nanowires could play a key role in controlling their adverse effects to organisms, as has been widely confirmed by studies on spherical nanomaterials (Nam and An 2019;Majumdar et al 2019;Riviere et al 2018). To the best of our knowledge, less than 15 studies have been published in which the impact of physicochemical properties of nanowires on their toxic effects were examined.…”