L. A. Osminkina

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.

Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy.

Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50°C under relatively low nanoparticle concentrations (<1 mg/mL) and RF radiation intensities (1–5 W/cm2). For both types of nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

Photoluminescent biocompatible silicon nanoparticles for cancer theranostic applications

Silicon nanoparticles (SiNPs) obtained by mechanical grinding of porous silicon have been used for visualization of living cells in vitro. It was found that SiNPs could penetrate into the cells without any cytotoxic effect up to the concentration of 100 μg/ml. The cell cytoplasm was observed to be filled by SiNPs, which exhibited bright photoluminescence at 1.6 eV. SiNPs could also act as photosensitizers of the singlet oxygen generation, which could be used in the photodynamic therapy of cancer. These properties of SiNPs are discussed in view of possible applications in theranostics (both in therapy and in diagnostics).

Porous silicon nanoparticles as sensitizers for ultrasonic hyperthermia

Aqueous suspensions of porous silicon nanoparticles (NPs) with average size ∼100 nm and concentration ∼1 g/L undergo significant heating as compared with pure water under therapeutic ultrasonic (US) irradiation with frequencies of 1–2.5 MHz and intensities of 1–20 W/cm2. This effect is explained by taking into account the efficient absorption of US energy by NPs. The observed US-induced heating of biodegradable NPs is promising for applications in ultrasonic hyperthermia of tumors.

Evaluation of genotoxicity and reproductive toxicity of silicon nanocrystals.

Silicon crystal 2-5 nm nanoparticles in the form of 1-5-μ granules in water suspension were injected intraperitoneally in a single dose to male F1(CBA×C57Bl/6) mice or to outbred albino rats on days 1, 7, and 14 of gestation. Silicon crystal nanoparticles in doses of 5, 25, and 50 mg/kg exhibited no cytogenetic activity in mouse bone marrow cells after 24-h exposure and in doses of 5 and 25 mg/kg after 7 and 14-day exposure. A 24-h exposure to silicon nanoparticles in a dose of 5 mg/kg significantly increased DNA damage (detected by DNA comet assay) in bone marrow cells. In a dose of 50 mg/kg they considerably increased DNA damage in bone marrow and brain cells after exposure of the same duration. Silicon nanoparticles in doses of 5 and 50 mg/kg caused no genotoxic effects in the same cells after 3-h and in a dose of 5 mg/kg after 7-day exposure. Silicon crystal nanoparticles in a dose of 50 mg/kg caused death of 60-80% mice after exposure >24 h. Injected in a dose of 50 mg/kg on days 1, 7, and 14 of gestation, silicon crystal nanoparticles reduced body weight gain in pregnant rats and newborn rats at different stages of the experiment, but had no effect on other parameters of physical development of rat progeny and caused no teratogenic effects.

Optical properties of silicon nanowire arrays formed by metal-assisted chemical etching: evidences for light localization effect

We study the structure and optical properties of arrays of silicon nanowires (SiNWs) with a mean diameter of approximately 100 nm and length of about 1–25 μm formed on crystalline silicon (c-Si) substrates by using metal-assisted chemical etching in hydrofluoric acid solutions. In the middle infrared spectral region, the reflectance and transmittance of the formed SiNW arrays can be described in the framework of an effective medium with the effective refractive index of about 1.3 (porosity, approximately 75%), while a strong light scattering for wavelength of 0.3 ÷ 1 μm results in a decrease of the total reflectance of 1%-5%, which cannot be described in the effective medium approximation. The Raman scattering intensity under excitation at approximately 1 μm increases strongly in the sample with SiNWs in comparison with that in c-Si substrate. This effect is related to an increase of the light-matter interaction time due to the strong scattering of the excitation light in SiNW array. The prepared SiNWs are discussed as a kind of ‘black silicon’, which can be formed in a large scale and can be used for photonic applications as well as in molecular sensing.

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 800 nm. 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.

Temperature responsive porous silicon nanoparticles for cancer therapy - spatiotemporal triggering through infrared and radiofrequency electromagnetic heating.

One critical functionality of the carrier system utilized in targeted drug delivery is its ability to trigger the release of the therapeutic cargo once the carrier has reached its target. External triggering is an alluring approach as it can be applied in a precise spatiotemporal manner. In the present study, we achieved external triggering through the porous silicon (PSi) nanoparticles (NPs) by providing a pulse of infrared or radiofrequency radiation. The NPs were grafted with a temperature responsive polymer whose critical temperature was tailored to be slightly above 37°C. The polymer coating improved the biocompatibility of the NPs significantly in comparison with their uncoated counterparts. Radiation induced a rapid temperature rise, which resulted in the collapse of the polymer chains facilitating the cargo release. Both infrared and radiofrequency radiation were able to efficiently trigger the release of the encapsulated drug in vitro and induce significant cell death in comparison to the control groups. Radiofrequency radiation was found to be more efficient in vitro, and the treatment efficacy was verified in vivo in a lung carcinoma (3LL) mice model. After a single intratumoral administration of the carrier system combined with radiofrequency radiation, there was clear suppression of the growth of the carcinoma and a prolongation of the survival time of the animals. TOC IMAGE The temperature responsive (TR) polymer grafted on the surface of porous silicon nanoparticles (PSi NPs) changes its conformation in response to the heating induced by infrared or radiofrequency radiation. The conformation change allows the loaded doxorubicin to escape from the pores, achieving controlled drug release from TR PSi NPs, which displayed efficacy against malignant cells both in vitro and in vivo.

Enhanced photoluminescence of porous silicon nanoparticles coated by bioresorbable polymers

A significant enhancement of the photoluminescence (PL) efficiency is observed for aqueous suspensions of porous silicon nanoparticles (PSiNPs) coated by bioresorbable polymers, i.e., polylactic-co-glycolic acid (PLGA) and polyvinyl alcohol (PVA). PSiNPs with average size about 100 nm prepared by mechanical grinding of electrochemically etched porous silicon were dispersed in water to prepare the stable suspension. The inner hydrophobic PLGA layer prevents the PSiNPs from the dissolution in water, while the outer PVA layer makes the PSiNPs hydrophilic. The PL quantum yield of PLGA/PVA-coated PSiNPs was found to increase by three times for 2 weeks of the storage in water. The observed effect is explained by taking into account both suppression of the dissolution of PSiNPs in water and a process of the passivation of nonradiative defects in PSiNPs. The obtained results are interesting in view of the potential applications of PSiNPs in bioimaging.

Studies of silicon nanoparticles uptake and biodegradation in cancer cells by Raman spectroscopy

In-vitro Raman micro-spectroscopy was used for diagnostics of the processes of uptake and biodegradation of porous silicon nanoparticles (SiNPs) in breast cancer cells (MCF-7 cell line). Two types of nanoparticles, with and without photoluminescence in the visible spectral range, were investigated. The spatial distribution of photoluminescent SiNPs within the cells obtained by Raman imaging was verified by high-resolution structured-illumination optical microscopy. Nearly complete biodegradation of SiNPs inside the living cells was observed after 13days of the incubation. The results reveal new prospects of multi-modal visualization of SiNPs inside cancer cells for theranostic applications.