A. A. Kudryavtsev

Silicon Nanocrystals As Photosensitizers of Active Oxygen for Biomedical Applications

Silicon nanocrystals dispersed in water have been used to photosensitize the generation of active oxygen. The photosensitizing efficiency has been estimated through the quenching of the exciton photoluminescence of silicon nanocrystals. Experiments have revealed a strong (up to 80%) decrease in the number of cancer mouse fibroblast cells when they come into contact with photoexcited silicon nanocrystals. The obtained results show that the use of silicon nanocrystals for biomedical applications, in particular, for photodynamic therapy of cancer, is feasible.

Nanoparticles prepared from porous silicon nanowires for bio-imaging and sonodynamic therapy

Evaluation of cytotoxicity, photoluminescence, bio-imaging, and sonosensitizing properties of silicon nanoparticles (SiNPs) prepared by ultrasound grinding of porous silicon nanowires (SiNWs) have been investigated. SiNWs were formed by metal (silver)-assisted wet chemical etching of heavily boron-doped (100)-oriented single crystalline silicon wafers. The prepared SiNWs and aqueous suspensions of SiNPs exhibit efficient room temperature photoluminescence (PL) in the spectral region of 600 to 1,000xa0nm that is explained by the radiative recombination of excitons confined in small silicon nanocrystals, from which SiNWs and SiNPs consist of. On the one hand, in vitro studies have demonstrated low cytotoxicity of SiNPs and possibilities of their bio-imaging applications. On the other hand, it has been found that SiNPs can act as efficient sensitizers of ultrasound-induced suppression of the viability of Hep-2 cancer cells.

Laser-synthesized oxide-passivated bright Si quantum dots for bioimaging.

Crystalline silicon (Si) nanoparticles present an extremely promising object for bioimaging based on photoluminescence (PL) in the visible and near-infrared spectral regions, but their efficient PL emission in aqueous suspension is typically observed after wet chemistry procedures leading to residual toxicity issues. Here, we introduce ultrapure laser-synthesized Si-based quantum dots (QDs), which are water-dispersible and exhibit bright exciton PL in the window of relative tissue transparency near 800u2009nm. Based on the laser ablation of crystalline Si targets in gaseous helium, followed by ultrasound-assisted dispersion of the deposited films in physiological saline, the proposed method avoids any toxic by-products during the synthesis. We demonstrate efficient contrast of the Si QDs in living cells by following the exciton PL. We also show that the prepared QDs do not provoke any cytoxicity effects while penetrating into the cells and efficiently accumulating near the cell membrane and in the cytoplasm. Combined with the possibility of enabling parallel therapeutic channels, ultrapure laser-synthesized Si nanostructures present unique object for cancer theranostic applications.

Lowering of the cavitation threshold in aqueous suspensions of porous silicon nanoparticles for sonodynamic therapy applications

A significant decrease of the cavitation threshold in aqueous suspensions of porous silicon nanoparticles (PSi NPs) with sizes about 100u2009nm as compared with pure water was observed for ultrasound irradiation (USI) with therapeutic frequency (0.88 MHz) and intensities (about 1u2009W/cm2). This effect is explained by porous morphology of PSi NPs, which promotes the nucleation of cavitation bubbles. In vitro experiments revealed a suppression of the proliferation of cancer cells with the introduced PSi NPs after exposure to USI related to the enhanced cavitation processes, which led to the cell destruction. The obtained results demonstrate that PSi NPs are prospective for applications as sonosensitizers in mild cancer therapy.

Effects of Nanostructurized Silicon on Proliferation of Stem and Cancer Cell

In vitro experiments showed that stem and cancer cells retained their viability on the surface of porous silicon with 10-100 nm nanostructures, but their proliferation was inhibited. Silicon nanoparticles of 100 nm in size obtained by mechanical grinding of porous silicon films or crystal silicon plates in a concentration below 1 mg/ml in solution did not modify viability and proliferation of mouse fibroblast and human laryngeal cancer cells. Additional ultrasonic exposure of cancer cells in the presence of 1 mg/ml silicon nanoparticles added to nutrient medium led to complete destruction of cells or to the appearance of membrane defects blocking their proliferation and initiating their apoptotic death.

Linear and Non-Linear Optical Imaging of Cancer Cells with Silicon Nanoparticles

New approaches for visualisation of silicon nanoparticles (SiNPs) in cancer cells are realised by means of the linear and nonlinear optics in vitro. Aqueous colloidal solutions of SiNPs with sizes of about 10–40 nm obtained by ultrasound grinding of silicon nanowires were introduced into breast cancer cells (MCF-7 cell line). Further, the time-varying nanoparticles enclosed in cell structures were visualised by high-resolution structured illumination microscopy (HR-SIM) and micro-Raman spectroscopy. Additionally, the nonlinear optical methods of two-photon excited fluorescence (TPEF) and coherent anti-Stokes Raman scattering (CARS) with infrared laser excitation were applied to study the localisation of SiNPs in cells. Advantages of the nonlinear methods, such as rapid imaging, which prevents cells from overheating and larger penetration depth compared to the single-photon excited HR-SIM, are discussed. The obtained results reveal new perspectives of the multimodal visualisation and precise detection of the uptake of biodegradable non-toxic SiNPs by cancer cells and they are discussed in view of future applications for the optical diagnostics of cancer tumours.

Silicon Nanoparticles as Amplifiers of the Ultrasonic Effect in Sonodynamic Therapy

The possibility of using mesoporous silicon nanoparticles as amplifiers (sensitizers) of therapeutic ultrasonic exposure were studied experimentally in vitro and in vivo. The combination of nanoparticles and ultrasound led to a significant inhibition of Hep-2 cancer cell proliferation and Lewis lung carcinoma growth in mice. These results indicated good prospects of using silicon nanoparticles as sensitizers for sonodynamic therapy of tumors.

Cytotoxicity control of silicon nanoparticles by biopolymer coating and ultrasound irradiation for cancer theranostic applications

Silicon nanoparticles (SiNPs) prepared by mechanical grinding of luminescent porous silicon were coated with a biopolymer (dextran) and investigated as a potential theranostic agent for bioimaging and sonodynamic therapy. Transmission electron microscopy, photoluminescence and Raman scattering measurements of dextran-coated SiNPs gave evidence of their enhanced stability in water. In vitro experiments confirmed thexa0lower cytotoxicity of the dextran-coated NPsxa0in comparison with uncoated ones, especially forxa0high concentrations of about 2 mg ml-1. Efficient uptake of the NPsxa0by cancer cells was found using bioimaging in the optical transmittance and photoluminescence modes. Treatmentxa0of the cells with uptaken SiNPs by therapeutic ultrasound for 5-20 min resulted in a strong decrease inxa0the number ofxa0living cells, while the total number of cells remained nearly unchanged. The obtained data indicate a mild effect of the combined action of ultrasonic irradiationxa0and SiNPs on cancer cells. The observed results reveal new opportunities forxa0controlling the photoluminescent and sonosensitizing properties of silicon-based NPsxa0for applications in the diagnostics and mild therapy of cancer.

Antimicrobial Effect of Biocompatible Silicon Nanoparticles Activated Using Therapeutic Ultrasound

In this study, we report a method for the suppression of Escherichia coli (E. coli) vitality by means of therapeutic ultrasound irradiation (USI) using biocompatible silicon nanoparticles as cavitation sensitizers. Silicon nanoparticles without (SiNPs) and with polysaccharide (dextran) coating (DSiNPs) were used. Both types of nanoparticles were nontoxic to Hep 2 cells up to a concentration of 2 mg/mL. The treatment of bacteria with nanoparticles and application of 1 W/cm2 USI resulted in the reduction of their viabilities up to 35 and 72% for SiNPs and DSiNPs, respectively. The higher bacterial viability reduction for DSiNPs as compared with SiNPs can be explained by the fact that the biopolymer shell of the polysaccharide provides a stronger adhesion of nanoparticles to the bacterial surface. Transmission electron microscopy (TEM) studies showed that the bacterial lipid shell was partially perforated after the combined treatment of DSiNPs and USI, which can be explained by the lysis of bacterial membrane due to the cavitation sensitized by the SiNPs. Furthermore, we have shown that 100% inhibition of E. coli bacterial colony growth is possible by coupling the treatments of DSiNPs and USI with an increased intensity of up to 3 W/cm2. The observed results reveal the application of SiNPs as promising antimicrobial agents.