Georgy S. Terentyuk

Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy

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.

Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery.

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.

Analytical and Theranostic Applications of Gold Nanoparticles and Multifunctional Nanocomposites

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.

Nanocomposites Containing Silica-Coated Gold–Silver Nanocages and Yb–2,4-Dimethoxyhematoporphyrin: Multifunctional Capability of IR-Luminescence Detection, Photosensitization, and Photothermolysis

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.

Gold nanorods with a hematoporphyrin-loaded silica shell for dual-modality photodynamic and photothermal treatment of tumors in vivo

AbstractNanocomposites (NCs) consisting of a gold nanorod core and a mesoporous silica shell doped with hematoporphyrin (HP) have been fabricated in order to improve the efficiency of cancer treatment by combining photothermal and photodynamic therapies (PDT + PTT) in vivo. In addition to the long-wavelength plasmon resonance near 810–830 nm, the fabricated NCs exhibited a 400-nm absorbance peak corresponding to bound HP, generated singlet oxygen under 633-nm excitation near the 632.5-nm Q-band, and produced heat under a 808-nm near-infrared (NIR) laser irradiation. These modalities were used for a combined PDT + PTT treatment of large (about 3 cm3) solid tumors in vivo with a xenorafted tumor rat model. NCs were directly injected into tumors and irradiated simultaneously with 633-nm and 808-nm lasers to stimulate the combined photodynamic and photothermal activities of NCs. The efficiency of the combined therapy was evaluated by optical coherence tomography, histological analysis, and by measurements of the tumor volume growth during a 21-day period. The NC-mediated PDT led to weak changes in tissue histology and to a moderate 20% decrease in the tumor volume. In contrast, the combined PDT + PTT treatment resulted in the large-area tumor necrosis and led to dramatic decrease in the tumor volume.

Plasmonic nanopowders for photothermal therapy of tumors.

We describe a novel strategy for the fabrication of plasmonic nanopowders (dried gold nanoparticles) by using wet chemical nanoparticle synthesis, PEG-SH functionalization, and a standard freeze-drying technique. Our strategy is illustrated by successful fabrication of different plasmonic nanopowders, including gold nanorods, gold-silver nanocages, and gold nanospheres. Importantly, the dried nanoparticles can be stored for a long time under usual conditions and then can easily be dissolved in water at a desired concentration without such hard manipulations as sonication or heating. Redispersed samples maintain the plasmonic properties of parent colloids and do not form aggregates. These properties make pegylated freeze-dried gold nanoparticles attractive candidates for plasmonic photothermal therapy in clinical settings. In this work, redispersed gold nanorods were intravenously administered to mice bearing Ehrlich carcinoma tumors at doses of 2 and 8 mg (Au)/kg (animal). Particle biodistribution was measured by atomic absorption spectroscopy, and tumor hyperthermia effects were studied under laser NIR irradiation. Significant tumor damage was observed only at the higher dose of the nanorods.

Silver nanocubes and gold nanocages: Fabrication and optical and photothermal properties

The paper presents experimental data on fabrication, optical, and photothermal properties of silver nanocubes and gold-silver nanostructures based on silver cube templates. The silver cubes were obtained using polyol synthesis with a sulfide-mediated reduction of silver nitrate by ethylene glycol in the presence of poly(vinyl pyrrolidone). A galvanic replacement method was used to fabricate gold-silver nanoparticles of various structures, starting from silver-gold alloy particles and ending by target gold nanocages. The gold nanocages formation was controlled by shifts of the extinction and differential light scattering plasmon resonances, the transmission and scanning electron microscopy, the electronic-spectroscopy analysis (ESI), the dark-field microscope light scattering, and by visual inspection of colloid colors. The comparative experimental data on the laser heating kinetics are presented for three particle types: gold nanorods, silica/gold nanoshells, and gold nanocages. For suspensions with equal optical density at the laser heating wavelength (near plasmon resonances at 800 nm), all three particle types revealed close photothermal parameters. However, the specific photothermal efficiency per metal particle mass was maximal for gold nanocages followed by gold nanorods and silica/gold nanoshells. A coupled dipole spheres method was used to calculate the extinction and absorption spectra of randomly oriented particles by an analytical solution for random orientation averaging. The nanoparticles were modeled by arrays of interacting spheres with small intersection and polarizability calculated through the first Mie coefficient. The measured and calculated extinction spectra of silver cubes and gold nanocages are in good agreement.

Optical coherence tomography monitoring of enhanced skin optical clearing in rats in vivo

Abstract. A comparative study of physical, chemical, and combined enhancement of transdermal transport of optical clearing agents (OCAs) is presented. As a physical enhancer of diffusivity, ultrasound (US) with a frequency 1 MHz and a power 1.1 W in the continuous mode was used, and dimethyl sulfoxide (DMSO) was used as a chemical enhancer. OCA (glycerol and polyethylene glycol-400 in equal proportion) was topically applied to the rat skin in vivo as alone or as together with the enhancers. Monitoring of skin optical clearing was implemented using an optical coherence tomography. The results have shown that the attenuation coefficient of intact skin dermis after the application of US-DMSO-OCA, US-OCA (both for 4 min), and DMSO-OCA (for 20 min) combinations decreased approximately by 31%, 19%, and 5%, respectively, while OCA alone did not induce a noticeable clearing effect for 20 min. Control skin sites with removed epidermis were used for modeling the upper limit of dermis optical clearing, i.e., maximal degree of optical clearing, by using the studied enhancers. They demonstrated that the attenuation coefficient decreases by 32%, 30%, 17%, and 16% at the action of US-DMSO-OCA, US-OCA, DMSO-OCA, and OCA, respectively. It can be concluded that US-DMSO-OCA combination only allowed reaching the upper limit of skin optical clearing.

Towards Effective Photothermal/Photodynamic Treatment Using Plasmonic Gold Nanoparticles

Gold nanoparticles (AuNPs) of different size and shape are widely used as photosensitizers for cancer diagnostics and plasmonic photothermal (PPT)/photodynamic (PDT) therapy, as nanocarriers for drug delivery and laser-mediated pathogen killing, even the underlying mechanisms of treatment effects remain poorly understood. There is a need in analyzing and improving the ways to increase accumulation of AuNP in tumors and other crucial steps in interaction of AuNPs with laser light and tissues. In this review, we summarize our recent theoretical, experimental, and pre-clinical results on light activated interaction of AuNPs with tissues and cells. Specifically, we discuss a combined PPT/PDT treatment of tumors and killing of pathogen bacteria with gold-based nanocomposites and atomic clusters, cell optoporation, and theoretical simulations of nanoparticle-mediated laser heating of tissues and cells.

Photosensitizer-loaded electrospun chitosan-based scaffolds for photodynamic therapy and tissue engineering.

Novel chitosan-based nanofibrous composite materials containing different amounts of the photosensitizer Photosens were obtained by electrospinning and were characterized by scanning electron microscopy and by confocal laser scanning microscopy. The release of Photosens from the materials was investigated in water and in phosphate-buffered saline. A noncancerous (MC3T3-E1 murine osteoblasts) and a cancerous [T-47D (mammary gland)] cell line were cultivated on Photosens-containing scaffolds, and cell growth and metabolic activity were examined by confocal laser scanning microscopy and by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide assay, respectively. The viability of both cell lines on Photosens-containing fibers decreased in a spatial manner upon laser irradiation of an appropriate wavelength and power density. Interestingly, the noncancerous MC3T3-E1 cells grown on Photosens -containing scaffolds were less affected by the irradiation. We conclude that the Photosens-containing electrospun chitosan nanofibers described here are of potential interest for biomedical applications, particularly topical photodynamic therapy and tissue engineering.