Near Infrared Absorbing Nanoparticles for Photothermal Cancer Therapy

Abstract

Advances in nanotechnology are expected to lead to the development of new and improved therapeutic strategies, amenable to targeting, that may ultimately revolutionize cancer treatment. For example, we have developed a nanoparticle-based photothermal cancer therapy that has shown high efficacy with virtually no damage to normal tissues (Hirsch et al., 2003, O’Neal et al., 2004, Lowery et al., 2006). This therapeutic strategy employs nanoparticles called nanoshells that are designed to strongly absorb near infrared (NIR) light. Metal nanoshells are a new type of nanoparticle composed of a dielectric (for instance, silica) core coated with an ultrathin metallic (for instance, gold) layer. Gold nanoshells possess physical properties similar to gold colloid, in particular, a strong optical absorption due to the collective electronic response of the metal to light. The optical absorption of gold colloid yields a brilliant red color that has been of considerable utility in consumer-related medical products, such as home pregnancy tests. In contrast, the optical response of gold nanoshells depends dramatically on the relative size of the nanoparticle core and the thickness of the gold shell. By varying the relative core and shell thicknesses, the color of gold nanoshells can be varied across a broad range of the optical spectrum that spans the visible and the near infrared spectral regions (Oldenburg et al., 1999). Gold nanoshells can be made to either preferentially absorb or scatter light at their plasmon resonance by varying the size of the particle relative to the wavelength of the light at their optical resonance. For cancer therapy, nanoshells are injected intravenously and allowed to accumulate in tumor sites due to the leakiness of the vasculature (EPR) and/or molecular targeting. Accumulation in the tumor sites peaks after several hours, at which time the tissue region is illuminated with NIR light for several minutes. NIR light is not absorbed to a significant extent by tissue components, but is strongly absorbed by nanoshells within the tumor. This leads to rapid heating of the tumor tissue without damage to adjacent normal tissues. In preliminary studies, complete tumor regression and 100% survival with no regrowth has been achieved. Mice with CT26 colon carcinoma tumors (4 mm diameter) were injected intravenously with NIR absorbing nanoshells that were coated with PEG-SH. 6 hr following nanoshell injection, the tumor sites were illuminated with light from a 820 nm diode laser (4 W/cm2) for 4 min. Animals in a sham group received a saline injection instead of nanoshells prior to NIR treatment, while a control group was untreated. Tumor size and animal survival were then tracked. As shown in Figure 1, all tumors treated with nanoshells had completely regressed within 10 days of treatment, while sham and control tumors had grown dramatically. Furthermore, all sham and control animals died within 20 days of treatment, while all nanoshell-treated mice continue to live (+12 months) with no tumor regrowth (Figure 2, O’Neal et al., 2004). Excellent nanoshell biocompatibility has been observed.