(489w) Stable Gold Nanorod-Based Assemblies and Matrices: Multifunctional Cancer Therapeutics, Optical Sensors, and Scaffolds

Gold nanoparticles possess a number of attractive properties including enhanced surface electric field, high biocompatibility, and ease of chemical conjugation. Consequently, gold nanoparticles are being increasingly investigated as potential therapeutics, drug delivery vehicles, imaging agents and diagnostics as part of the expanding field of nanomedicine. In particular, gold nanorods demonstrate a tunable photothermal response to near infrared (NIR) light have been employed for the ablation of cancer cells, biomolecule detection and the generation of functional nanoscale assemblies. First, we demonstrate the formation of gold nanorod (GNR)-elastin-like polypeptide (ELP) nanoassemblies whose optical response can be remotely controlled based on near-infrared (NIR) light exposure. In this study, cysteine-containing ELPs (C2ELP) were self ?assembled on gold nanorods (GNRs) leading to GNR- C2ELP nanoassemblies. Exposure of GNR- C2ELP assemblies to NIR laser resulted in the heating of GNRs due to surface plasmon resonance. Heat transfer from the GNRs resulted in a temperature increase of the self-assembled C2ELP above its transition temperature (Tt), leading to a detectable phase transition and aggregation of the GNR- C2ELP assemblies. This phase transition was quantified using an optical readout, based on an increase in the optical density of the GNR- C2ELP dispersion. This optical response was seen only in the case of GNR- C2ELP nanoassemblies. While a photothermal response was observed in the case of a dispersion consisting of GNRs alone, no optical response could be seen due to the absence of the C2ELP. In addition C2ELP solutions demonstrated neither a photothermal nor an optical response. The reproducibility and reversibility of optical response of GNR- C2ELP nanoassemblies was demonstrated across multiple cycles following exposure and removal of the laser irradiation. Second, we employed the layer-by-layer deposition of recently generated cationic polymers in our laboratory in order to increase the short-term and long-term stability of gold nanorods in biological media, phosphate buffered saline (PBS), serum-free media (SFM) and serum-containing media (SCM). Polyelectrolyte-coated gold nanorods exhibit excellent long term optical stability in all three biologically media even after four weeks of storage. In addition, stabilization of the optical response resulted in a reliable, Arrhenius-like photothermal response of the well-dispersed gold nanorods over the period of investigation. Cytotoxicity evaluation indicated that gold nanorods coated with our polymers were less cytotoxic to mammalian cells than those covered with 25-kDa polyethyleneimine (pEI25). Stable and biocompatible polyelectrolyte-coated nanorods were successfully employed for the photothermal ablation of PC3-PSMA cells using NIR laser irradiation. In addition, sub-toxic concentrations of these nanorods were also employed for delivering plasmid DNA to these cells. Our results indicate that molecular engineering of cationic polyelectrolytes can lead to stable, biocompatible gold nanorod assemblies that can be useful for a variety of applications including non-viral gene delivery and cancer cell photothermal ablation. In summary, our results indicate that polypeptides and polyelectrolytes can be interfaced with GNRs resulting in optically responsive nanoassemblies and increase in stability. We anticipate that these nanoassemblies can be useful for sensing, tissue engineering, and drug delivery applications.