(5bm) Multilayer Dielectric Core-Gold Shell Nanoparticles: a Platform for Microscale Applications Including Localized Plasmonic Heating and Targeted Therapeutics

Recently, dielectric core/metallic shell composite nanoparticles have shown promise as potential drug delivery vehicles. They can be activated remotely via near infrared (NIR) laser pulses, taking advantage of the plasmonic heating due to the high absorption of the metal nanoshells relative to that of the dielectric particle core, as well as the surrounding tissues and media which are comparatively transparent in that frequency range. Previously, our group demonstrated that 300 mJ of NIR (730 nm) femtosecond laser irradiation of core-shell silica-gold (SiO2-Au) nanoparticles induced extreme local heating sufficient to remove the silica core, leaving an incomplete gold shell behind, which could be further broken into nanoparticles by additional heating. Here, we report on the use of polymers as the core in these composite particles. Initially polystyrene cores were used because they allow for facile fictionalization and gold nanoshell growth. Preliminary efforts with other polymer polyelectrolyte cores will also be discussed. The coverage of the gold nanoshells as they grow can be monitored sequentially by UV/vis/NIR spectroscopy, TEM, and light scattering. The interaction and stability of these particles in different dispersing media is significant, since the ultimate goal is application in media significantly more complex than DI water. The particle stability was greatly reduced by the presence of electrolytes due to the decrease in Debye lengths. The addition of a thiolated 5 kDa polyethylene glycol (PEG) layer attached to the gold nanoshell provided a steric stabilizing effect to the particle dispersions that was relatively independent of electrolyte concentration. We found that subjecting these composite particles to several minutes duration of 730 nm femptosecond 150 mJ laser pulses was sufficient to cause swelling of the polymer core and distortion of the gold nanoshell without destroying the composite particles completely. Higher energy irradiation caused complete disruption of the particles. The PEG outer layer may also have provided increased strength to the composite particle and acted as a heat sink since the PEG itself is relatively transparent to such wavelengths. It is also expected to potentially reduce protein adsorption and opsonization in vivo, thereby prolonging circulation. Without further conjugation or modification this PEG covered composite particle should allow for potential passive targeting to sites with poor vasculature, such as tumors, where extravasation of particles can lead to their accumulation in the tumor area. Bioconjugation of the PEG outer surface could allow for more active site specific targeting. Others have shown that such laser irradiation to similar core-shell particles can be used for inducing localized tissue hyperthermia. Encapsulation of drugs or therapeutic agents into these particles could provide the potential for site specific delivery upon low energy laser irradiation.