We describe an application of plasmonic silica/gold nanoshells to produce a controllable laser hyperthermia in tissues with the aim of the enhancement of cancer photothermal therapy. Laser irradiation parameters are optimized on the basis of preliminary experimental studies using a test-tube phantom and laboratory rats. Temperature distributions on the animal skin surface at hypodermic and intramuscular injection of gold nanoparticle suspensions and affectations by the laser radiation are measured in vivo with a thermal imaging system. The results of temperature measurements are compared with tissue histology.

Kinetics, biodistribution, and histological studies were performed to evaluate the particle-size effects on the distribution of 15 nm and 50 nm PEG-coated colloidal gold (CG) particles and 160 nm silica/gold nanoshells (NSs) in rats and rabbits. The above nanoparticles (NPs) were used as a model because of their importance for current biomedical applications such as photothermal therapy, optical coherence tomography, and resonance-scattering imaging. The dynamics of NPs circulation in vivo was evaluated after intravenous administration of 15 nm CG NPs to rabbit, and the maximal concentrations of gold were observed 15-30 min after injection. Rats were injected in the tail vein with PEG-coated NPs (about 0.3 mg Au/kg rats). 24 h after injection, the accumulation of gold in different organs and blood was determined by atomic absorption spectroscopy. In accordance with the published reports, we observed 15 nm particles in all organs with rather smooth distribution over liver, spleen and blood. By contrast, the larger NSs were accumulated mainly in the liver and spleen. For rabbits, the biodistribution was similar (72 h after intravenous injection). We report also preliminary data on the light microscopy and TEM histological examination that allows evaluation of the changes in biotissues after gold NPs treatment.

Laser-nanoparticle interaction is crucial for biomedical applications of lasers and nanotechnology to the treatment of cancer or pathogenic microorganisms. We report on the first observation of laser-induced coloring of gold nanoshell solution after a one nanosecond pulse and an unprecedentedly low bubble formation (as the main mechanism of cancer cell killing) threshold at a laser fluence of about 4 mJ cm(-2), which is safe for normal tissue. Specifically, silica/gold nanoshell (140/15 nm) suspensions were irradiated with a single 4 ns (1064 nm) or 8 ns (900 nm) laser pulse at fluences ranging from 0.1 mJ cm(-2) to 50 J cm(-2). Solution red coloring was observed by the naked eye confirmed by blue-shifting of the absorption spectrum maximum from the initial 900 nm for nanoshells to 530 nm for conventional colloidal gold nanospheres. TEM images revealed significant photomodification of nanoparticles including complete fragmentation of gold shells, changes in silica core structure, formation of small 20-30 nm isolated spherical gold nanoparticles, gold nanoshells with central holes, and large and small spherical gold particles attached to a silica core. The time-resolved monitoring of bubble formation phenomena with the photothermal (PT) thermolens technique demonstrated that after application of a single 8 ns pulse at fluences 5-10 mJ cm(-2) and higher the next pulse did not produce any PT response, indicating a dramatic decrease in absorption because of gold shell modification. We also observed a dependence of the bubble expansion time on the laser energy with unusually very fast PT signal rising (∼3.5 ns scale at 0.2 J cm(-2)). Application of the observed phenomena to medical applications is discussed, including a simple visual color test for laser-nanoparticle interaction.

No abstract

Confocal laser scanning microscopy (CLSM) is a modern high-resolution optical technique providing detailed image of tissue structure with high (down to microns) spatial resolution. Aiming at a concurrent improvement of imaging depth and image quality the CLSM requires the use of contrast agents. Commonly employed fluorescent contrast agents, such as fluorescent dyes and proteins, suffer from toxicity, photo-bleaching and overlapping with the tissues autofluorescence. Gold nanoparticles are potentially highly attractive to be applied as a contrast agent since they are not subject to photo-bleaching and can target biochemical cells markers associated with the specific diseases. In current report we consider the applicability of gold nanospheres as a contrast agent to enhance quality of CLSM images of skin tissues in vitro versus the application of optical clearing agent, such as glycerol. The enhancement of CLSM image contrast was observed with an application of gold nano-spheres diffused within the skin tissues. We show that optical clearing agents such as a glycerol provide better CLSM image contrast than gold nano-spheres. μmEnhancement of CLSM image contrast of skin tissues after application of gold nanoparticles as a contrast agent