Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: Potential for cancer therapy

Abstract

Background and Objective: We developed a new approach that enhances selective photothermolysis of tumor through laser activation of synergistic phenomena around nanoclusters, which are self-assembled into cancer cells. Study Design/Materials and Methods: In vitro verification of this approach was performed by laser pulse irradiation (420-570 nm and 1064 nm; 8-12 nanosecond; 0.1-10 J/cm2) of MDA-MB-231 breast cancer cells targeted with primary antibodies to which 40-nm gold nanoparticles were selectively attached by means of secondary antibodies. Photothermal (PT) radiometry, thermolens techniques, electron microscopy, atomic force microscopy, silver and gold enhancing kits, and viability test (Annexin V-propidium iodide) were employed to study nanoparticle spatial organization, the dynamics of microbubble formation, and cell damage. Results: The assembly of gold nanoclusters on the cell membrane was accompanied by increased local absorption and red-shifting as compared to cells that did not have nanoclusters. These effects were amplified by a silver-enhancing kit and pre-irradiation of cells with low laser-pulse energy. Finally, a significant increase in laser-induced bubble formation and cancer cell killing was observed using near-IR lasers (1064 nm). A cancer cell antigens was used to provide target specificity for nanoclusters formation making the cancer cells sensitive to laser activation. Conclusion: The described approach uses relatively small and simple gold nanoparticles offering more effective delivery to target. In addition, the further self-assembling of these nanoparticles into nanoclusters on live cells provides significant enhancement of laser-induced cell damage. These nanoclusters (gold "nanobombs") can be activated in cancer cells only by confining near-IR laser pulse energy within the critical mass of the nanoparticles in the nanoclusters. © 2005 Wiley-Liss, Inc.