B83

Photothermal cancer therapy using targeted nanoshells may enable the preferential destruction of cancer cells while minimizing damage to healthy tissue. Nanoshells possess an optical tunability that spans the near infrared (NIR) - a region where light penetrates tissues deeply. Conjugated with tumor-targeting molecules, NIR absorbing nanoshells could be systemically injected and preferentially bound to tumor sites. NIR light heats the tumor-bound nanoshells, thus destroying the tumor. In vitro and in vivo studies confirmed the ability to selectively induce cell death with the photothermal interaction of nanoshells and NIR light. Previous studies demonstrated the ability of PEG-coated nanoshells to passively accumulate at a tumor site. Complete regression of tumors was observed in animals receiving systemic injections of nanoshells prior to NIR laser treatment. Furthermore, the tissue damage from the NIR laser therapy was confined to the tissue region receiving both nanoshells and laser irradiation. Nanoshells can be targeted to cancer cells or tumor vasculature by the conjugation of tumor specific antibodies to the gold surface. These targeted nanoshells may increase the cellular specificity of nanoshell binding and improve the therapeutic results.Gold nanoshells were manufactured as previously described. Briefly, silica cores were fabricated by the reduction of tetraethoxysilane in ethanol. Following amine functionalization, gold colloid was adsorbed to silica surface. Reduction of additional gold completes the shell. The nanoshells used in the following study had a 110 nm core diameter with a 10 nm thick gold shell and a peak extinction at ~820 nm. Soluble vascular endothelial growth factor (VEGF) was conjugated to the gold nanoshells through a bifunctional PEG linker, containing N-hydroxy succihimide for coupling and an orthopyridyl-disulfide for attachment to the gold surface.In vitro, targeted nanoshells were incubated with murine endothelial cells at 2.9x109 particles/mL. Unbound nanoshells were rinsed from the surface with PBS and replaced with fresh medium. Control cells were incubated with PEG-coated nanoshells without targeting molecules. After exposure to NIR light (820 nm, 1.55 W, 1.5 mm diameter spot, for 7 min), the cells were incubated overnight at 37oC. Cell viability was assessed by staining with calcein AM. Nanoshells were visualized by silver staining.Cell death was confined within the laser spot for cells incubated with properly targeted nanoshells. Silver staining verified the presences of nanoshells. Control nanoshells did not bind to the cells, as indicated by silver staining, and control cells continued to be viable after irradiation. Nanoshells show promise as a minimally invasive cancer therapy. The nanoshells are biocompatible and display selective photothermal destruction of tissue by absorption of NIR light. Targeting may improve the cellular specificity of the nanoshell therapy.

[First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, Sep 12-15, 2006]