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.

Gold nanoparticles (GNPs) and GNP-based multifunctional nanocomposites are the subject of intensive studies and biomedical applications. This minireview summarizes our recent efforts in analytical and theranostic applications of engineered GNPs and nanocomposites by using plasmonic properties of GNPs and various optical techniques. Specifically, we consider analytical biosensing; visualization and bioimaging of bacterial, mammalian, and plant cells; photodynamic treatment of pathogenic bacteria; and photothermal therapy of xenografted tumors. In addition to recently published reports, we discuss new data on dot immunoassay diagnostics of mycobacteria, multiplexed immunoelectron microscopy analysis of Azospirillum brasilense, materno-embryonic transfer of GNPs in pregnant rats, and combined photodynamic and photothermal treatment of rat xenografted tumors with gold nanorods covered by a mesoporous silica shell doped with hematoporphyrin.

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.

We describe novel composite nanoparticles consisting of a gold-silver nanocage core and a mesoporous silica shell functionalized with the photodynamic sensitizer Yb-2,4-dimethoxyhematoporphyrin (Yb-HP). In addition to the long-wavelength plasmon resonance near 750-800 nm, the composite particles exhibited a 400-nm absorbance peak and two fluorescence peaks, near 580 and 630 nm, corresponding to bound Yb-HP. The fabricated nanocomposites generated singlet oxygen under 630-nm excitation and produced heat under laser irradiation at the plasmon resonance wavelength (750-800 nm). In particular, we observed enhanced killing of HeLa cells incubated with nanocomposites and irradiated by 630-nm light. Furthermore, an additional advantage of fabricated conjugates was an IR-luminescence band (900-1060 nm), originating from Yb(3+) ions of bound Yb-HP and located in the long-wavelength part of the tissue transparency window. This modality was used to control the accumulation and biodistribution of composite particles in mice bearing Ehrlich carcinoma tumors in a comparative study with intravenously injected free Yb-HP molecules. Thus, these multifunctional nanocomposites seem an attractive theranostic platform for simultaneous IR-luminescence diagnostic and photodynamic therapy owing to Yb-HP and for plasmonic photothermal therapy owing to Au-Ag nanocages.

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