Nanophotothermolysis of cancer cells
Nanophotothermolysis using pulsed lasers and absorbing nanoparticles (e.g., gold nanospheres, nanorods, or carbon nanotubes) attached to specific targets has recently demonstrated considerable potential for selective damage to cancer cells,1,2 bacteria,3 and perhaps viruses.3 The temperature of gold nanoparticles (GNs) irradiated by short laser pulses rises very quickly, hypothetically reaching thresholds for nonlinear effects such as microbubble formation, and acoustic and shock wave generation, creating irreparable damage to targets. However, other than bubble formation, which requires a liquid environment, there continues to be little detailed discussion of the mechanisms around an overheated GN. In particular, for targets that lack sufficient liquid, including dense solid tumor, bones, and atherosclerotic plaques, bubble formation is not efficient.
We have investigated the role of photothermal-based effects, exclusive of bubble formation around overheated GNs in cell damage, with a focus on thermal explosion4 of GNs—known as nanobombs—delivered to the cells. Such explosions occur when heat is generated within the strongly absorbing target more rapidly than it diffuses. Two possible physical mechanisms could lead to the laser-induced explosion of nanoparticles: thermal explosion through electron-phonon excitation-relaxation, and Coulomb explosion through multiphoton ionization. A phenomenological picture of these complex physical effects is shown schematically in Figure 1.
In the spectral range of GN surface plasmon resonance absorption, Eexpl (the threshold energy density for thermal explosion of nanoparticles) can be estimated from simple energy balance, by which the total energy absorbed by the GN during its inertial retention in the vapor state (explosion time) is equal to the energy required for complete evaporation of the GN. Our calculations4 show that for the particular laser performances used in experiments5 (λ=532nm, τL=8–10ns), Eexpl=38.5mJ/cm2 for thermal explosion of a solid gold nanosphere of size R=35nm. Eexpl depends strongly on the types of nanoparticles (e.g., gold solid nanospheres, nanoshells, or nanorods). Due to higher plasmon-resonance absorption efficiency of nanorods, the threshold energy fluence can be reduced by using gold nanorods up to Eexpl=11mJ/cm2. We should note that the estimated thresholds are the lower limit of Eexpl obtained for ideal conditions.
The estimated values for Eexpl are in good agreement with various available experimental results. Indeed, for spherical GNs with an average size 45nm and irradiated with second-harmonic Nd:YAG (neodymium-doped yttrium aluminum garnet) laser pulses (532nm for 7ns), the laser fluence thresholds for changing the GN shape and its fragmentation phenomena are 16 and 30mJ/cm2, respectively.6 For a 30ps pulse, 25nm GN fragmentation has been observed at 23mJ/cm2, with a slight effect on changing GN shape, even at 2–5mJ/cm2.7
The laser-induced explosion effect can explain our experimental results, which include notable cancer cell damage with 1.4nm GNs inside viruses on a membrane with picosecond laser pulses (30ps, 50–100mJ/cm2) when the probability of classic water bubble formation is very low.8 We believe that the explosion mode may be essential in selective nanophotothermolysis of DNA,3,8 and this mode is definitely becoming dominant in the absence of a sufficient amount of water around GNs.
This work was supported in part by the US Army Research Office under contract W911NF-04-1-0383 and NIH/NIBIB grants EB000873 and EB005123.
Dr. Renat Letfullin is an assistant professor in the Department of Physics and Optical Engineering at the Rose-Hulman Institute of Technology. A noted theoretician and experimentalist in the fields of optics and lasers, he has recently branched out into biophotonics and nanomedicine. He has published over 100 refereed journal articles and conference proceedings, including three book chapters.
Prof. Charles Joenathan is presently professor and chair of the Department of Physics and Optical Engineering at the Rose-Hulman Institute of Technology. He has been an Alexander von Humboldt fellow and worked closely with researchers in universities and laboratories in Germany, Switzerland, Argentina, and Holland. He is a fellow of OSA and OSI, and SPIE, and a member of ASEE. He has published over 120 scientific articles in the field of holography and speckle applications, holographic optical elements, electronic speckle pattern interferometry, fiber optic sensors, and optical data processing.
Prof. Vladimir Zharov, PhD, DSc, served as professor and chairman of the Biomedical Engineering Department at the Moscow State Technical University from 1988 to 1999. In 2000, he moved to the University of Arkansas for Medical Sciences (UAMS) as director of Philips Classic Laser Laboratories, and also professor and director of laser research at UAMS. His work is in the field of laser spectroscopy and medicine. He has published more than 150 papers and five books.
Prof. Thomas F. George serves as chancellor and professor of chemistry and physics at the University of Missouri-St. Louis. His research deals with theoretical studies of materials and optical physics, with special interest in nanoscience. He has been a member of SPIE since 1979 and was named a SPIE Fellow in 1994.
