Selection of stabilizing agents to provide effective penetration of gold nanoparticles into cells

Abstract Objective: Gold nanorods are known to be promising agents for photothermal therapy. But the uptake of rod-shaped nanoparticles is lower than their spherical counterpart. It was therefore the objective of this study to select gold nanoparticles (GNPs)-stabilizing agents in order to provide effective penetration into cancer cells. Materials and methods: The work was carried out on human ovarian adenocarcinoma SKOV-3 cells. The gold nanorods used in this work had a plasmon resonance peak at 800 nm. The nanoparticles were stabilized by Pluronic® F-127 (PF127), chitosan or polyethylene glycol (PEG); the latter with 6000 Da and 40,000 Da molecular weight. Penetration and intracellular distribution of GNPs were investigated by transmission electron microscopy (TEM) and two-photon luminescence microscopy (2PLM) techniques. Results: By means of 2PLM and TEM, it could be shown that PF127 facilitates cellular uptake of GNPs very effectively. PF127-stabilized GNPs rapidly (by 1.5 h) penetrated the cell membrane and into the cytoplasm and cell nucleus. GNPs stabilized by chitosan were slowly internalized by the cells in smaller amount. GNPs stabilized by PEG with different molecular weights had difficulty to penetrate into the cells – GNPs were localized on the outer side of the cell membrane after short incubation, and single agglomerates were found in the cells after an extended incubation time. Conclusion: Nanoparticles stabilized with PF127 were the most effective nanoparticles to penetrate into the cells and were located in the cytoplasm and cell nuclei. Nanoparticles stabilized with chitosan were internalized into cells at a slower rate and in smaller amounts than those stabilized with PF127. Nanoparticles stabilized with PEG6000 Da and PEG40.000 Da were located mainly on cell membranes and could be found in the cytoplasm only after a longer incubation time.