Plasmonically Targeted Laser Treatment of Human Endothelial Cells

Abstract

The potential of small metal nanoparticles for converting resonant light into local heat has given rise to new applications in biomedicine [1]. While many studies focus on destructive laser hyperthermia of malignant cancer cells, the impact of photothermal therapies using plasmonic nanoparticles on healthy, primary human cells is of interest for controlling biological functions and for combined, dual-action treatments. Here, we present results on the controlled laser treatment of human endothelial cells (HUVECs) using oligo-ethylene glycol (OEG-)coated nanoparticles, which are either specifically targeted using peptide-functionalization, or which are nonspecifically taken up by the cells without further functionalization [2-4]. Peptide-functionalized nanoparticles were found to specifically bind to VEGF-receptors in the cell membrane [2]. Subsequent laser treatment at mild conditions of up to 30 W/cm2laser intensity resulted in partially reversible damage of the cellular membrane. A remarkable recovery of cells was found within 24 hours following treatment [3]. For non-functionalized nanoparticles, combined ICP-OES analysis and numerical modeling indicated that irreversible cell apoptosis was caused by collective heating effects over the illumination spot (Fig. 1, left panel) [3]. It is argued that the multiscale effects of nanoparticle hyperthermia range from single nanoparticles to collective heating of macroscopic areas, and on time scales from picoseconds to seconds, are an important factor in designing effective nanoparticle treatments. New studies explore plasmonic laser treatment on in-vitro angiogenesis, the organisation of endothelial cells into a network of microvessels (Fig.1, right panel). [1] Dreaden, E. C., Alkilany, A. M., Huang, X., Murphy, C. J., and El-Sayed, M. A., Chem. Soc. Rev., 41, 2740-2779 (2012); Barreto, J. A., O'Malley, W., Kubeil, M., Graham, B., Stephan, H., Spiccia, L., Adv. Mater., 23, H18-H40 (2011). [2] Bartczak D, Sanchez-Elsner T., Louafi F., Millar T., Kanaras A. G., Small 7, 388–394 (2011). [3] D. Bartczak, O. L. Muskens, T. M. Millar, T. Sanchez-Elsner, A. G. Kanaras, Nano Lett. 11, 1358-1363 (2011). [4] D. Bartczak, O. L. Muskens, S. Nitti, T. Sanchez-Elsner, T. M. Millar, and A. G. Kanaras, Small 8, 122-130 (2012). Figure 1 (left panel) Calculated temperature increase caused by a single nanoparticle (left) and integrated over the 500mm illumination spot (right) [4]. (right panel) In-vitro angiogenesis of HUVECs in a MDA cancer-cell medium.