The Impact of PEGylation on Cellular Uptake and In Vivo Biodistribution of Gold Nanoparticle MRI Contrast Agents

Abstract

Gold nanoparticles (GNPs) have immense potential in biomedicine, but understanding their interactions with serum proteins is crucial as it could change their biological profile due to the formation of a protein corona, which could then affect their ultimate biodistribution in the body. Grafting GNPs with polyethylene glycol (PEG) is a widely used practice in research in order to decrease opsonization of the particles by serum proteins and to decrease particle uptake by the mononuclear phagocyte system. We investigated the impact of PEGylation on the formation of protein coronae and the subsequent uptake by macrophages and MDA-MB-231 cancer cells. Furthermore, we investigated the in vivo biodistribution in xenograft tumor-bearing mice using a library of 4 and 10 nm GNPs conjugated with a gadolinium chelate as MRI contrast agent, cancer-targeting aptamer AS1411 (or CRO control oligonucleotide), and with or without PEG molecules of different molecular weight (Mw: 1, 2, and 5 kDa). In vitro results showed that PEG failed to decrease the adsorption of proteins; moreover, the cellular uptake by macrophage cells was contingent on the different configurations of the aptamers and the length of the PEG chain. In vivo biodistribution studies showed that PEG increased the uptake by tumor cells for some GNPs, albeit it did not decrease the uptake of GNPs by macrophage-rich organs.

Evaluation of Radiosensitization and Cytokine Modulation by Differentially PEGylated Gold Nanoparticles in Glioblastoma Cells

“…Escaping macrophage uptake beneficially improves GNP blood circulation time and thereby improves delivery to target sites such as tumours [ 26 , 27 ]. In addition, PEGylation is also known to reduce the number of protein interactions during circulation to favourably lower GNP aggregation and liver accumulation, and, ultimately, achieve elimination [ 28 ]. Therefore, we hypothesise that the PEGylated GNPs, potentially by reduced opsonisation, have enhanced stability and improved cellular uptake.…”

The menace of severe adverse events and deaths associated with viral gene therapy and its potential solution

“…[57][58][59] Incubating gold NP with human serum results in protein corona formation and increases NP phagocytosis by macrophages. 60 As protein coronas may not only alter NP circulation time but also mask targeting moieties, a number of strategies preventing corona formation have been developed. [61][62][63][64] These include PEGylation, coating NP with other polymers (e.g., zwitterionic polymers), and careful NP design.…”

Internalization of Pegylated Er:Y2O3 Nanoparticles inside HCT-116 Cancer Cells: Implications for Imaging and Drug Delivery

“…It is therefore necessary to suitably functionalize them in order to reduce their toxicity and to use them for biological applications. Coating the surface of nanoparticles with polyethylene glycol, known as “PEGylation”, is a common approach to make systems more soluble and to reduce capture by the reticuloendothelial system. , This process definitely improves the circulation in bloodstream, the internalization, and the accumulation at tumor sites . It is also extremely important to use nanoparticles of the appropriate size to facilitate internalization inside cells.…”