title: Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: potential for cancer therapy.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Philips Classic Laser Laboratories, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. ZharovVladimirP@uams.edu
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zharov
authors.forename: Elena N
authors.initials: EN
authors.lastname: Galitovskaya
authors.forename: Carl
authors.initials: C
authors.lastname: Johnson
authors.forename: Thomas
authors.initials: T
authors.lastname: Kelly
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000912:Antibodies, Neoplasm / Q000528:radiation effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D006046:Gold / Q000528:radiation effects / Q000627:therapeutic use; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D028022:Low-Level Light Therapy / Q000379:methods*; D008670:Metals / Q000528:radiation effects / Q000627:therapeutic use; D049329:Nanostructures / Q000528:radiation effects*; D010789:Phototherapy / Q000379:methods
chemical_list: D000912:Antibodies, Neoplasm; D008670:Metals; D006046:Gold