Irina L. Maksimova

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.

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.

Controlling optical properties of sclera

Transscleral laser microsurgery has gained wide acceptance recently. Many problems in this field are due to laser beam decay in an optically nonhomogeneous sciera. The sciera light transmission in defined by scattering processes on its fibers. Because of high density in the arrangement of sciera fibers, the phenomena of interferential interaction between scattered radiation and multiple scattering are essential. Our paper is aimed at the theoretical and experimental validation of light scattering decrease on collagen fibers by substituting the sciera base substance with substance exhibiting higher refraction index. As a model of sciera, system of long dielectric cylinders was chosen, which were surrounded by isotropic base substance with lower refraction index. The fibril diameters are varied from 10 to 100 nm. The indexes of refraction for the fibrils and embedding substance differ appreciably from each other and are equal2, respectively) to 1,47 and 1.345. The thickness of sciera is I mm. The statistic characteristics of spatial arrangement of fiber centers were described at an approximation of exduded volume. The scattering amplitude function for a single cylinder was calculated using Mie theory. Under calculation it was assumed that the axes of all the fibers are parallel to the sciera surface and their orientation in this plane is random. Two complex coefficients for waves, polarized in parallel and normally to the fiber axes, were found by means of method describing the propagation of coherent waves through random systems. According to this approach, scattering medium is represented as homogeneous but a having new effective refraction index. The imaginary part of the index takes into account energy extinction due to scattering.

The effect of multiple scattering in disperse media on polarization characteristics of scattered light

The effect of scattering of different multiplicity on polarization characteristics of scattered light is studied by the Monte Carlo computer simulation technique. The scattering multiplicity distribution versus the direction of scattering and dimensions of the scattering system is obtained for monodisperse systems of spherical particles of different size. The angular dependences of the elements of the light-scattering matrix (LSM) are calculated. It is shown that in a system of spherical particles, specific features of the LSM structure associated with multiple scattering have much in common with similar features of the LSM in systems of nonspherical particles under conditions of single scattering. The angular dependences of the degree of depolarization of the scattered light are studied.

Investigation of Mueller matrices of anisotropic nonhomogeneous layers in application to an optical model of the cornea

We consider a system of anisotropic layers as an optical model of the eye cornea. Effective refraction indices for normally incident light are calculated with the assumption that each layer consists of closely packed uniform cylinders (fibrils). Jones matrix formalism is used to describe light propagation through the cornea. We calculate the Jones matrices from the experimentally measured Mueller matrices. Two algorithms are used for this purpose. The experiments have shown that ~20% of cornea area studied had the structure well described by the helical model proposed.

Application of gold nanoparticles to X-ray diagnostics and photothermal therapy of cancer

We describe applications of colloidal gold nanoparticles and silica/gold nanoshells to photothermal therapy and X-ray diagnostics of cancer exemplified by spontaneous tumor of cats and dog. It is shown that the contrast of X-ray images of a cat mammalian tumor can be increased significantly by injection of 3-5-nm gold nanoparticles. We also present preliminary results of a complex approach to treatment a dog mouth cavity melanoma by using immunotherapy together with laser photothermolysis enhanced with silica/gold nanoshells.

Control of optical properties of biotissues: I. spectral properties of the eye sclera

A method for computer modeling of transmission and diffuse reflection of a strongly scattering biotissue is described. Results of calculations of spectral characteristics for a model of the human eye sclera are presented and compared with experiments. The possibility to control optical properties of biotissues is theoretically substantiated and experimentally confirmed. Variations in color indices of biotissues are calculated using theoretical and experimental spectral characteristics obtained for the eye sclera.

Cancer laser therapy using gold nanoparticles

Abstract: In the chapter we describe the possibilities for enhancement of the efficacy of laser selective photothermolysis and hyperthermia mediated by gold nanoparticles (of various shape/size and surface modification) for treatment of tumors. It is shown that unique optical properties of plasmon-resonant nanoparticles open new applications in photothermal therapy. The absorption coefficient of gold nanoparticles near the plasmon resonance is four/six orders of magnitude greater than that of other organic labels and photosensitizers. In addition, gold nanoparticles are photostable and nontoxic, and they can be easily conjugated to antibodies or proteins.