No abstract

Plasmonic nanoparticles have shown promise in hyperthermic cancer therapy, both in vitro and in vivo. Previous reports have described hyperthermic ablation using targeted and non-targeted nanoparticles internalized by cancer cells, but most reports do not describe a theoretical analysis for determining optimal parameters. The focus of the current research was first to evaluate the spatiotemporal temperature distribution and cell death induced by extracellular hyperthermia in which gold nanorods (GNRs) were maintained in the dispersion outside human prostate cancer cells. The nanorod dispersion was irradiated with near infrared (NIR) laser and the spatiotemporal distribution of temperature was determined experimentally. This information was employed to develop and validate theoretical models of spatiotemporal temperature profiles for gold nanorod dispersions undergoing laser irradiation, and the impact of the resulting heat generation on the viability of human prostate cancer cells. A cell injury/death model was then coupled to the heat transfer model to predict spatial and temporal variations in cell death and injury. The model predictions agreed well with experimental measurements of both, temperature and cell death profiles. Finally, the model was extended to examine the impact of selective binding of gold nanorods to cancer cells compared to non-malignant cells, coupled with a small change in cell injury activation energy. The impact of these relatively minor changes results in a dramatic change in the overall cell death rate. Taken together, extracellular hyperthermia using gold nanorods is a promising strategy and tailoring the cellular binding efficacy of nanorods can result in varying therapeutic efficacies using this approach.

The propensity of nanoparticles to aggregate in aqueous media hinders their effective use in biomedical applications. Gold nanorods (GNRs) have been investigated as therapeutics, imaging agents, and diagnostics. We report that chemically generated gold nanorods rapidly aggregate in biologically relevant media. Depositing polyelectrolyte multilayers on gold nanorods enhanced the stability of these nanoparticles for at least up to four weeks. Dispersions of polyelectrolyte (PE)-gold nanorod assemblies (PE-GNRs) demonstrate a stable Arrhenius-like photothermal response, which was exploited for the hyperthermic ablation of prostate cancer cells in vitro. Sub-toxic concentrations of PE-GNR assemblies were also employed for delivering exogenous plasmid DNA to prostate cancer cells. PE-GNRs based on a cationic polyelectrolyte recently synthesized in our laboratory demonstrated higher transfection efficacy and lower cytotoxicity compared to those based on polyethyleneimine, a current standard for polymer-mediated gene delivery. Our results indicate that judicious engineering of biocompatible polyelectrolytes leads to multifunctional gold nanorod-based assemblies that combine high stability and low cytotoxicity with photothermal ablation, gene delivery, and optical imaging capabilities on a single platform.