Olga Bibikova

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.

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.

THE EXPERIMENTAL STUDY OF STRESS-RELATED PATHOLOGICAL CHANGES IN CEREBRAL VENOUS BLOOD FLOW IN NEWBORN RATS ASSESSED BY DOCT

In experiments on newborn rats with stress-related intracranial hemorrhage (ICH) using Doppler optical coherence tomography (DOCT) we have shown that latent stage of ICH (4 h after stress) is characterized by decrease of venous blood outflow and the loss of sensitivity of sagittal vein to vasoconstrictor effect of adrenaline. The incidence of ICH (24 h after stress) was accompanied by progression of early pathological changes in cerebral venous blood flow (CVBF) and development of venous insufficiency. Taking into consideration of this fact, we suggest that the suppression of CVBF related to the severity to the deleterious effect of stress on the brain hemodynamics in newborn rats. These facts allow us to conclude that the venous insufficiency with the loss of vasoconstrictor response to adrenaline is an informative and sensitive component of pattern of CVBF that can be important diagnostic criteria of risk of ICH development in newborns.

Optical properties of plasmon-resonant bare and silica-coated nanostars used for cell imaging

Abstract. We synthesized and characterized gold nanostars and their silica-coated derivatives with 7- to 50-nm shell thicknesses as contrast agents for optical imaging. The scattering and absorption coefficients of the nanoparticles (NPs) were estimated by means of collimated transmittance and diffuse reflectance/transmittance analyses. The contrasting properties of the nanostructures were studied in optical coherence tomography glass capillary imaging. The silica-coated nanostars with the thickest shell have higher scattering ability in comparison with bare nanostars. Viability assays confirmed weak in vitro toxicity of nanostructures at up to ∼200-μg/mL concentrations. We showed real-time visualization of nanostars in both agarose and cultured cells by analyzing the backscattering signal using a conventional laser confocal microscope. The signal intensity detected from the silica-coated NPs was almost 1.5 times higher in comparison with bare nanostars. To the best of our knowledge, this is the first time that conventional laser confocal microscopy was applied in combined scattering and transmitted light modes to detect the backscattered signal of gold nanostars, which is useful for direct monitoring of the uptake, translocation, and accumulation of NPs in living cells.

New Types of Nanomaterials: Powders of Gold Nanospheres, Nanorods, Nanostars, and Gold-Silver Nanocages

We describe a new strategy for the fabrication of plasmonic nanopowders (dried gold or composite nanoparticles) by using wet chemical nanoparticle synthesis, PEG-SH functionalization, and freeze drying. This strategy is illustrated by the successful production of four plasmonic nanopowders, including gold nanorods, nanostars, gold-silver nanocages, and gold nanospheres. The dried nanoparticles can be stored for a long time under ordinary conditions and then easily dissolved in water at a desired concentration without heating, intense sonication, or other harsh treatments. According to the MTT assay with SPEV-2 cells, gold nanorod powder is not toxic at concentrations up to 100 mg/L. Redispersed samples maintain the plasmonresonant properties of the parent colloids and do not form aggregates. These properties make pegylated freeze-dried gold nanoparticles (GNPs) applicable in various fields of biomedicine.

Plasmon-Resonant Gold Nanostars With Variable Size as Contrast Agents for Imaging Applications

Plasmon-resonant nanostars (NSts) have recently found applications in biophotonics due to their unique optical and chemical characteristics, showing comparable or superior properties than other anisotropic plasmon-resonant nanoparticles. In this paper, we synthesized gold NSts by the seed-mediated surfactant-free method. By varying the diameters and amount of spherical seeds we tuned the final NSts tip-to-tip sizes to 50, 82, 100, and 120 nm ensuring the plasmon-resonant peak location between 710 and 830 nm, and the scattering/absorption ratio at the plasmon-resonant wavelengths being 0.12, 0.25, 0.30, 0.35 correspondingly. We investigated the application of the NSts as contrast agents for imaging techniques operating at visible and infrared wavelengths: optical coherence tomography (OCT) and Doppler OCT with the spectrum centered at 930-nm wavelength, as well as for conventional confocal laser scanning microscopy (CLSM) working at 633 nm. The most intense OCT signal was registered from the largest NSts, in correspondence with spectroscopy measurements at 930-nm wavelength. For imaging of nanoparticles incubated with living cells, we applied CLSM in combined scattering and transmission modes, and observed localization of the NSts on the cell surface. Due to the highest scattering at the CLSM operating wavelength, the strongest signal was obtained from the 82-nm particles; the lowest intensity of the CLSM backscattered signal was detected from the cells labeled with the smallest NSts. Thus, by tuning the initial concentration of seeds, it is possible to adjust the size (and scattering properties) of the nanostars to the operating wavelength of the optical device to achieve the best performance.

WAVELET-BASED ANALYSIS OF CEREBROVASCULAR DYNAMICS IN NEWBORN RATS WITH INTRACRANIAL HEMORRHAGES

Intracranial hemorrhage (IH) is a major problem of neonatal intensive care. The incidence of IH is typically asymptomatic and cannot be effectively detected by standard diagnostic methods. The mechanisms underlying IH are unknown but there is evidence that stress-induced disorders in adrenergic regulation of cerebral venous blood flow (CVBF) are among the main reasons. Quantitative and qualitative assessment of CVBF could significantly advance understanding of the nature of IH in newborns. In this work, we analyze variations of CVBF in newborn rats with an experimental model of stress-induced IH and adrenaline injection. Our analysis is based on the Doppler optical coherence tomography (DOCT) and a proposed adaptive wavelet-based approach that provides sensitive markers of abnormal reactions of the sagittal vein to external factors. The obtained results demonstrate that the incidence of IH in newborn rats is accompanied by a suppression of CVBF with the development of venous insufficiency and areactivity to adrenaline. We introduce a numerical measure θ, quantifying reactions of CVBF and show that the values θ < 1.23 estimated in the low-frequency (LF) spectral range corresponding to the sympathicus indicate abnormal reactions associated with the development of IH. We conclude that the revealed areactivity of the cerebral veins to adrenaline represents a possible mechanism responsible for pathological changes in CVBF.

Plasmon-Resonant Gold Nanoparticles with Variable Morphology as Optical Labels and Drug Carriers for Cytological Research

In this work, two types of nanocomposites, silica-coated nano-sea-urchins and silica-coated gold nanostars, were fabricated. CTAB-coated nano-sea-urchins with an average size of about 100 nm demonstrate an absorption peak near 600-700 nm and stability in aqueous suspension. CTAB was exchanged with m-PEG-SH by an intermediate PEG layer. A layer of silica was synthesized on the nano-sea-urchins surface with thickness of about 20 nm. Nanostars with an average size of about 60 nm with a number of thin sharp branches were fabricated and functionalized by PVP to improve their stability. PVP-coated nanostars were used in optical coherence tomography experiments to show their contrasting properties. After silica-coating, stable and monodispersed nanoparticles with silica shell thickness about 60 nm were obtained. Nontoxicity of the silica-coated nanostars at least until the concentration of nanoparticles about 400 μg/mL was showed by fluorescent cell viability assay using propidium iodide. Extinction coefficient of the gold nanostars and nanocomposites was estimated by a spectrophotometer system in collimated transmission regime.

Gold nanostructures for OCT imaging of capillary flow

In this paper, plasmon-resonant nanostructures, such as gold nanostars and their silica-coated composites, were used for enhancement of OCT image contrast of water flows in glass capillaries. The contrasting properties of the synthesized nanostars and nanocomposites with silica shell thickness of about 5 nm and 50 nm were compared in the framework of capillary stasis model. The most intensive signal was detected from the nanocomposites with the thickest silica shell. The nanocomposites were characterized by optical spectroscopy and electron microscopy. Nontoxicity of nanostars and nanocomposites up to ~ 3 mg/mL concentration was showed by MTT assay suggesting practical applications of the nanostructures for bioimaging.

High-resolution deep-tissue optical imaging using anti-Stokes phosphors

We report on the high-resolution deep-tissue imaging using novel water-dispersible upconversion nanoparticles (UCNPs) β-NaYF4:Yb3+:Tm3+. Luminescence from the UCNP embedded into tissue-mimicking phantoms at the depth of 4 mm epi-illuminated with 975-nm laser radiation was detected. Fiber-optic detection shows 2-times better resolution compared with that obtained using CCD-based imaging modality. The conversion efficiency of upconversion particles and their cytotoxicity to HeLa cells were also investigated and reported.