Cellular uptake and cytotoxicity of PEGylated gold nanoparticles in C33A cervical cancer cells

Abstract

Gold nanoparticles (GNPs) have served as an excellent candidate for biomedical applications. GNPs can be conjugated with carboxyl-polyethylene glycol-thiol (PEG) as a stealth coating which prolongs circulation time [Lipka J et al 2010 Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials, 31, 6574-6581, Janát-Amsbury M et al 2011 Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. Eur. J. Pharm. Biopharm, 77, 417-423] and increases cellular uptake.[He B et al 2017 Increased cellular uptake of peptide-modified PEGylated gold nanoparticles. Biochem. Biophys. Res. Commun., 494, 339-345, Soenen S. J et al 2014, The cellular interactions of PEGylated gold nanoparticles: effect of PEGylation on cellular uptake and cytotoxicity. Part. Part. Syst. Charact., 31, 794-800, Guo J et al 2016 Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells. Int. J. Pharm., 509, 16-27. Brandenberger C et al 2010 Quantitative evaluation of cellular uptake and trafficking of plain and polyethylene glycol-coated gold nanoparticles. Small, 6, 1669-1678. To examine the biological effects of PEG-coated GNPs, we investigated their cytotoxicity on human cervical cancer C33A cells as compared to citrate-capped GNPs. Our results indicated that PEGylated GNPs markedly induce apoptosis and necrosis causing cell shrinkage and cell membrane asymmetry. 30 nm citrate-capped GNPs were synthesized in aqueous solution using a citrate-reduction method. GNPs were functionalized with PEG (MW = 7500 g mol-1. The GNPs were characterized using scanning electron microscopy (SEM), confirming that the as-synthesized GNPs have a diameter of 30 nm. Dynamic light scattering (DLS) determined that the hydrodynamic diameter of PEGylated GNPs was 78.82 nm, and that of citrate-capped GNPs was 43.82 nm. Zeta potential measurements showed an increase in colloidal stability for PEGylated GNPs as compared to citrate GNPs, with a zeta potential of-33.33 mV observed for citrate-capped GNPs and a zeta potential of-43.38 mV observed for PEGylated GNPs. The PEGylated GNPs were found to effectively induce early and late-stage apoptosis in C33A cells with a significant reduction in total cell viability of 32.3%. Based on the apoptotic activity in C33A cells, PEGylated GNPs may serve as a promising radiosensitizer for cancer treatments.