Targeted sonocatalytic cancer cell injury using avidin-conjugated titanium dioxide nanoparticles

In this study, we applied sonodynamic therapy to cancer cells based on the delivery of titanium dioxide (TiO₂) nanoparticles (NPs) modified with avidin protein, which preferentially discriminated cancerous cells from healthy cells. Subsequently, hydroxyl radicals were generated from the TiO₂ NPs after activation by external ultrasound irradiation (TiO₂/US treatment). Although 30% of the normal breast cells (human mammary epithelial cells) exhibited the uptake of avidin-modified TiO₂ NPs, over 80% of the breast cancer cells (MCF-7) exhibited the uptake of avidin-TiO₂ NPs. Next the effect of the TiO₂/US treatment on MCF-7 cell growth was examined for up to 96 h after 1-MHz ultrasound was applied (0.1 W/cm², 30 s) to cells that incorporated the TiO₂ NPs. No apparent cell injury was observed until 24 h after the treatment, but the viable cell concentration declined to 68% compared with the control at 96 h.     

A simple route to prepare stable hydroxyapatite nanoparticles suspension

A simple ultrasound assisted precipitation method with addition of glycosaminoglycans (GAGs) is proposed to prepare stable hydroxyapatite (HAP) nanoparticles suspension from the mixture of Ca(H₂PO₄)₂ solution and Ca(OH)₂ solution. The product was characterized by XRD, FT-IR, TEM, HRTEM and particle size, and zeta potential analyzer. TEM observation shows that the suspension is composed of 10–20 nm × 20–50 nm short rod-like and 10–30 nm similar spherical HAP nanoparticles. The number-averaged particle size of stable suspension is about 30 nm between 11.6 and 110.5 nm and the zeta potential is −60.9 mV. The increase of stability of HAP nanoparticles suspension mainly depends on the electrostatic effect and steric effect of GAGs. The HAP nanoparticles can be easily transported into the cancer cells and exhibit good potential as gene or drug carrier system.     

Fe doping induced enhancement in room temperature ferromagnetism and selective cytotoxicity of CeO2 nanoparticles

In the present study, structural, optical, magnetic properties as well as cytotoxicity of undoped and Fe doped Ceria (CeO₂) nanoparticles synthesized by simple soft chemical method have been reported. SEM and XRD results have shown that the synthesized samples are comprised of ultrafine spherical nanoparticles having single phase cubic fluorite structure of CeO₂. Raman spectroscopy results have depicted a red shift in F_2g mode with Fe doping which reveals enhancement in the oxygen vacancies. The optical band gap calculated from UV–visible absorption spectra has been found to vary unsystematically with Fe doping which is associated with the creation of impurity level and abundance in oxygen vacancies with Fe doping. The oxygen vacancies have introduced the room temperature ferromagnetism (RTFM) in undoped and Fe doped CeO₂ nanoparticles. The saturation magnetization (M_s) value of pristine CeO₂ nanoparticles has been found to be 0.00083 emu/g which is increased up to 0.0126 emu/g for 7% Fe doped nanoparticles. For cytotoxicity tests, the synthesized nanoparticles induced effects on Neuroblastoma cancer cells & HEK-293 healthy cells have been analyzed via CCK-8 analysis. It has been observed that the prepared undoped and Fe doped CeO₂ nanoparticles have nontoxic nature towards healthy cells while they are extremely toxic towards cancerous cells. Furthermore, the anticancer activity is found to enhance with Fe doping. The selective toxicity and enhancement in anticancer activity with Fe doping has observed to be strongly correlated with reactive oxygen species (ROS) generation.     

Sonocatalytic injury of cancer cells attached on the surface of a nickel–titanium dioxide alloy plate

The present study demonstrates ultrasound-induced cell injury using a nickel–titanium dioxide (Ni–TiO₂) alloy plate as a sonocatalyst and a cell culture surface. Ultrasound irradiation of cell-free Ni–TiO₂ alloy plates with 1 MHz ultrasound at 0.5 W/cm² for 30 s led to an increased generation of hydroxyl (OH) radicals compared to nickel–titanium (Ni–Ti) control alloy plates with and without ultrasound irradiation. When human breast cancer cells (MCF-7 cells) cultured on the Ni–TiO₂ alloy plates were irradiated with 1 MHz ultrasound at 0.5 W/cm² for 30 s and then incubated for 48 h, cell density on the alloy plate was reduced to approximately 50% of the controls on the Ni–Ti alloy plates with and without ultrasound irradiation. These results indicate the injury of MCF-7 cells following sonocatalytic OH radical generation by Ni–TiO₂. Further experiments demonstrated cell shrinkage and chromatin condensation after ultrasound irradiation of MCF-7 cells attached on the Ni–TiO₂ alloy plates, indicating induction of apoptosis.     

Toxicity of amorphous silica nanoparticles in mouse keratinocytes

The present study was designed to examine the uptake, localization, and the cytotoxic effects of well-dispersed amorphous silica nanoparticles in mouse keratinocytes (HEL-30). Mouse keratinocytes were exposed for 24 h to various concentrations of amorphous silica nanoparticles in homogeneous suspensions of average size distribution (30, 48, 118, and 535 nm SiO₂) and then assessed for uptake and biochemical changes. Results of transmission electron microscopy revealed all sizes of silica were taken up into the cells and localized into the cytoplasm. The lactate dehydrogenase (LDH) assay shows LDH leakage was dose- and size-dependent with exposure to 30 and 48 nm nanoparticles. However, no LDH leakage was observed for either 118 or 535 nm nanoparticles. The mitochondrial viability assay (MTT) showed significant toxicity for 30 and 48 nm at high concentrations (100 μg/mL) compared to the 118 and 535 nm particles. Further studies were carried out to investigate if cellular reduced GSH and mitochondria membrane potential are involved in the mechanism of SiO₂ toxicity. The redox potential of cells (GSH) was reduced significantly at concentrations of 50, 100, and 200 μg/mL at 30 nm nanoparticle exposures. However, silica nanoparticles larger than 30 nm showed no changes in GSH levels. Reactive oxygen species (ROS) formation did not show any significant change between controls and the exposed cells. In summary, amorphous silica nanoparticles below 100 nm induced cytotoxicity suggest size of the particles is critical to produce biological effects.     

Cellular uptake and radiosensitization of SR-2508 loaded PLGA nanoparticles

SR-2508 (etanidazole), a hypoxic radiosensitizer, has potential applications in radiotherapy. The poly(d,l-lactide-co-glycolide)(PLGA) nanoparticles containing SR-2508 were prepared by w/o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The cellular uptake of the nanoparticles for the two human tumor cell lines: human breast carcinoma cells (MCF-7) and human carcinoma cervices cells (HeLa), was evaluated by fluorescence microscopy and transmission electronic microscopy. Cell viability was measured by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 90 nm and 190 nm. The encapsulation efficiency was 20.06%. The drug release pattern exhibited an initial burst followed by a plateau for over 24 h. The cellular uptake of nanoparticles was observed. Co-culture of MCF-7 and HeLa cells with SR-2508 loaded nanoparticles showed that released SR-2508 retained its bioactivity and effectively sensitized two hypoxic tumor cell lines to radiation. The radiosensitization of SR-2508 loaded nanoparticles was more significant than that of free drug.     

Synthesis of water-dispersible photoluminescent silicon nanoparticles and their use in biological fluorescent imaging

Water-dispersible silicon nanoparticles (Si-NPs) are desirable for applications in biological techniques. A simplified method to synthesize such particles is reported here. The resulting Si-NPs are water-dispersible and luminescent. Under the excitation of UV light, the Si-NPs emit strong red light with a peak maximum at 606 nm and a quantum yield of 6%. They are highly stable, and remain so over several weeks. Fourier Transform Infrared (FTIR) spectroscopy shows a visible Si–CH₂ scissoring vibration mode. Furthermore, the surface chemical bondings were confirmed by X-ray photoelectron spectroscopy (XPS). In the Si2p and C1s core levels, Si–C components are observed. The diameters of the synthesized Si-NPS as measured by atomic force microscope (AFM) are approximately 5 nm. Furthermore, the nanoparticles can be taken up by cultured cells. Fluorescence images of Si-NPs within MCF-7 human breast cancer cells show they are distributed throughout the cell tissue.     

Effect of pre-annealing on NO32- centers in synthetic hydroxyapatite

Effect of pre-annealing of synthetic hydroxyapatite (HAP) on properties of γ- and UV- induced NO₃^2- centers was studied by electron paramagnetic resonance (EPR). Nitrate-containing hydroxyapatite powders ((N)HAP)) and the powders with an admixture of carbonate and nitrate ions ((C,N)HAP) were annealed in the temperature range T_ann = 20 °C ? 600 °C before irradiation. It was found that pre-annealing of (N)HAP samples changes the parameters of NO₃^2- centers while no changes took place in (C,N)HAP. Moreover, at the pre-annealing temperatures T_ann > 200 °C two new NO₃^2- centers were observed in (N)HAP samples; they are characterized by larger value of A_⊥ (3.67 and 4.41 mT) as compared to the known centers. It was also found that the dependence of NO₃^2- centers amount on T_ann is non-monotonous in both types of samples. Presumably this is caused by the escape of water molecules from HAP during the annealing and essential modification of the defect subsystem of HAP.     

Protoporphyrin IX-mediated sonodynamic action induces apoptosis of K562 cells

Objectives

The present study aims to investigate apoptosis of human leukemia K562 cells induced by protoporphyrin IX (PpIX)-mediated sonodynamic therapy (PpIX-SDT).

Methods

The uptakes of intracellular PpIX in K562 cells were detected by flow cytometry. The sub-cellular localization of PpIX was imaged by confocal microscope. The cytotoxic effect of PpIX-SDT was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenylter-trazolium bromide tetrazolium) assay. Apoptosis was evaluated by chromatin condensation with DAPI (4′-6-diamidino-2-phenylindole) staining, decrease of mitochondria membrane potential (MMP), re-distribution of Bax, and the expression changes of the key apoptosis-associated protein (Caspase-3 and polypeptide poly (ADP-robose) polymerase). The possible mechanism of SDT-induced apoptosis was investigated by detecting by intracellular ROS (reactive oxygen species) generation and effect of ROS scavenger-NAC (N-acetylcysteine) on SDT induced apoptosis.

Results

The intracellular PpIX increased quickly within 2 h after PpIX administration and PpIX mainly localized in the mitochondria. Compared with PpIX alone and ultrasound alone groups, the synergistic cytotoxicity of PpIX plus ultrasound was significantly boosted. In addition, the ultrasound induced some extent of chromatin condensation and MMP loss was greatly enhanced by the presence of 2 μg/ml PpIX, where PpIX alone treatment showed no or only slight effect. Time-dependent Bax translocation, caspase-3 activation and PARP cleavage were detected in SDT treatment groups. Besides, intracellular ROS production was significantly enhanced after SDT, and the general ROS scavenger NAC could obviously alleviate the SDT-caused cell viability loss, MMP loss, Bax redistribution and nuclear changes.

Conclusions

These results indicated that PpIX-mediated sonodynamic action could induce apoptosis on K562 cells, and the intracellular ROS was involved in the PpIX-SDT induced apoptosis.     

Mitochondria-Targeted Bovine Serum Albumin@Copper Sulfide Nanocomposites Conjugated with Rhodamine-110 Dye for an Enhanced Efficacy of Cancer Photothermal Therapy

Recently, mitochondria-targeted photothermal nanoagents demonstrated an improved therapeutic efficacy of cancer cells, compared with non-targeting ones. Herein, copper sulfide (CuS) nanoparticles are in situ synthesized via bovine serum albumin (BSA) templates to prepare photothermal BSA@CuS nanocomposites with high efficiency (42.0%) of photothermal conversion. Subsequently, rhodamine-110 (R) molecules are covalently conjugated with BSA@CuS nanocomposites to construct mitochondria-targeted R-BSA@CuS nanocomposites, which still retained 22.8% of photothermal conversion efficiency. Furthermore, as-prepared R-BSA@CuS nanocomposites can be efficiently internalized by human breast cancer (MCF-7) cells, and then specifically accumulated in their subcellular mitochondria, not lysosomes. Compared with non-targeting BSA@CuS nanocomposites, these mitochondria-targeted R-BSA@CuS nanocomposites show a significant enhancement (***p < 0.001) of their anticancer efficacy under the same near-infrared irradiation conditions, whose mechanism is further explored in details. Finally, these R-BSA@CuS nanocomposites can succeed in penetrating in 3D multicellular tumor spheroids composed of MCF-7 cells. And they also show a significant inhibition effect (**p < 0.01) on the growth of spheroids via photothermal therapy, in contrast to bare BSA@CuS nanocomposites under the same irradiation conditions. Therefore, these mitochondria-targeted and photothermal R-BSA@CuS nanocomposites have important potential applications on cancer photothermal therapy with an enhanced efficacy.     

Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis

Catalytic nanoparticles represent a potential clinical approach to replace or correct aberrant enzymatic activities in patients. Several diseases, including many blinding eye diseases, are promoted by excessive oxidant stress due to reactive oxygen species (ROS). Cerium oxide and platinum nanoparticles represent two potentially therapeutic nanoparticles that de-toxify ROS. In the present study, we directly compare these two classes of catalytic nanoparticles. Cerium oxide and platinum nanoparticles were found to be 16 ± 2.4 and 1.9 ± 0.2 nm in diameter, respectively. Using surface plasmon-enhanced microscopy, we find that these nanoparticles associate with cells. Furthermore, cerium oxide and platinum nanoparticles demonstrated superoxide dismutase catalytic activity, but did not promote hemolytic or cytolytic pathways in living cells. Importantly, both cerium oxide and platinum nanoparticles reduce oxidant-mediated apoptosis in target cells as judged by the activation of caspase 3. The ability to diminish apoptosis may contribute to maintaining healthy tissues.     

Reciprocal Response of Human Oral Epithelial Cells to Internalized Silica Nanoparticles

Silica nanoparticles (SiO₂ NPs) are one of the most widely used engineered nanoparticles and can been found in a wide range of consumer products. Despite their massive global production scale, little is known about their potential effects in the context of unintended exposure or ingestion. Using TR146 cells as an in vitro model of the human oral buccal mucosa, the uptake, spatial intracellular distribution, reactive oxygen species (ROS) production, inflammatory response, and cytotoxic effects of commercial SiO₂ NPs are examined. SiO₂ NPs are shown to dock and cross the cellular membrane barrier in a dose–time‐dependent manner. Confocal sectioning reveals translocation of SiO₂ NPs into the cell nucleus after 12 h of exposure. A concentration threshold of more than 500 × 10^?6 m is observed, above which SiO₂ NPs are shown to exert significant oxidative stress with concomitant upregulation of inflammatory genes IL6 and TNFA. Further analysis of the p53 pathway and a series of apoptotic and cell cycle biomarkers reveals intracellular accumulation of SiO₂ NPs exert marginal nanotoxicity. Collectively, this study provides important information regarding the uptake, intracellular distribution, and potential adverse cellular effects of SiO₂ NPs commonly found in consumer products in the human oral epithelium.     

Studies on toxicity of aluminum oxide (Al<Subscript>2</Subscript>O<Subscript>3</Subscript>) nanoparticles to microalgae species: <Emphasis Type="Italic">Scenedesmus</Emphasis> sp. and <Emphasis Type="Italic">Chlorella</Emphasis> sp.

In view of increasing commercial applications of metal oxide nanoparticles their toxicity assessment becomes important. Alumina (Al₂O₃) nanoparticles have wide range of applications in industrial as well as personal care products. In the absence of prior report on toxicological impact of alumina nanoparticles to microalgae, the principal objective of this study was to demonstrate the effect of the nanoparticles on microalgae isolated from aquatic environment (Scenedesmus sp. and Chlorella sp.). The growth inhibitory effect of alumina nanoparticles was observed for both the species (72 h EC₅₀ value, 45.4 mg/L for Chlorella sp.; 39.35 mg/L for Scenedesmus sp.). Bulk alumina also showed toxicity though to a lesser extent (72 h EC₅₀ value, 110.2 mg/L for Chlorella sp.; 100.4 mg/L for Scenedesmus sp.). A clear decrease in chlorophyll content was observed in the treated cells compared to the untreated ones, more effect being notable in the case of nanoparticles. Preliminary results based on FT-IR studies, optical and scanning electron microscopic images suggest interaction of the nanoparticles with the cell surface.     

Pre-irradiation with low-dose <Superscript>12</Superscript>C<Superscript>6+</Superscript> beam significantly enhances the efficacy of <Emphasis Type="Italic">AdCMV-p53</Emphasis> gene therapy in human non-small lung cancer

The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOl of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6 beam induced AdCMV-p53 infected cells were more than 90%, which were significantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6 beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6 beam significantly improved cell to apoptosis. RBEs for the 12C6 AdCMV-p53 infection groups were 30%-60%, 20% -130% and 30%-70% more than those for the 12C6 -irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6 beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.     

Systematic evaluation of biocompatibility of magnetic Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> nanoparticles with six different mammalian cell lines

This article systematically evaluated the biocompatibility of multiple mammalian cell lines to 11-nm DMSA-coated Fe₃O₄ magnetic nanoparticles (MNPs). Cells including RAW264.7, THP-1, Hepa1-6, HepG2, HL-7702, and HeLa were incubated with six different concentrations (0, 20, 30, 40, 50, and 100 μg/mL) of MNPs for 48 h, and then the cell labeling, iron loading, cell viability, apoptosis, cycle, and oxidative stress were all quantitatively evaluated. The results revealed that all the cells were effectively labeled by the nanoparticles; however, the iron loading of RAW264.7 was significantly higher than that of other cells at any dose. The proliferations of all the cells were not significantly suppressed by MNPs at the studied dose except HepG2 that was exposed to 100 μg/mL MNPs. The investigation of oxidative stress demonstrated that the levels of total superoxide dismutase and xanthine oxidase had no significant changes in all the cells treated by all the doses of MNPs, while the levels of malonyldialdehyde activity of MNP-treated cells significantly increased. The nanoparticles did not produce any significant effect on cell cycles at any of the doses, but resulted in significant apoptosis of THP-1 and HepG2 cells at the highest concentration of 100 μg/mL. At a concentration of 30 μg/mL which was used in human studies with an intravascular nanoparticle imaging agent (Combidex), the nanoparticles efficiently labeled all the cells studied, but did not produce any significant influence on their viability, oxidative stress, and apoptosis and cycle. Therefore, the nanoparticles were concluded with better biocompatibility, which provided some useful information for its clinical applications.     

Iron Oxychloride/Bovine Serum Albumin Nanosheets as Chemodynamic Therapy Agents

Iron oxychloride (FeOCl) is known for reactive oxygen species (ROS) generation through Fenton chemistry. The activity of FeOCl is preserved in the slightly acidic pH value of the tumor microenvironment (pH 6.5−6.9). Such property can be advantageous in biobased systems, where ROS generation can be modulated in slightly acidic conditions, which is characteristic of the solid tumor microenvironment. In the present study, BSA-stabilized FeOCl nanosheets (NSs) are synthesized and characterized by transmission electron microscope, Fourier transform infrared spectroscopy, zeta potential analysis, dynamic light scattering, and UV–vis spectroscopy. The morphology of the nanoparticles is flake-like, and their hydrodynamic diameter is around 200 nm. MTT, apoptosis assay, and trypan blue staining evaluate the toxicity of FeOCl NSs toward the 4T1 cell line. It is found that the toxicity of the NSs is higher in physiological conditions of solid tumors (pH 6.5, H₂O₂ 100 × 10⁻⁶ m ) than in the conditions of healthy organs (pH 7.4). Specifically, cancer cells are in their late apoptotic stage by more than eight times higher at pH 6.5 than pH 7.4. The toxicity results are in agreement with the in vitro catalytic assay of the NSs. Therefore, the FeOCl NSs can be the building blocks for constructing chemodynamic therapy agents.     

Confocal Raman spectroscopy to monitor intracellular penetration of TiO2 nanoparticles

Confocal Raman microscopy, a noninvasive, label‐free, and high‐spatial resolution imaging technique, in combination with K‐mean cluster analysis and a correlation coefficient map, was employed to trace titanium dioxide (TiO₂) nanoparticles in living MCF‐7 and TERT cells. The penetration of TiO₂ nanoparticles into cells revealed a gradual time‐dependent diffusion of nanoparticles over the entire cell. Cell apoptosis was monitored by tracing cytochrome c diffusion into the cytoplasm. A comparison with the mitochondrial clustering indicated that cytochrome c was inside the mitochondria for TiO₂ concentration of 2 µg ml⁻¹. This result demonstrates that the presence of TiO₂ particles within a cell does not induce apoptosis. We demonstrated that confocal Raman microscopy allow to follow penetration of TiO₂ particles in cell and to monitor the apoptotic status of the penetrated cells. Copyright © 2014 John Wiley & Sons, Ltd.     

Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line

Background  

Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5). RGC-5 cells were cultured in a closed hypoxic chamber (5% O₂) with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH) assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38) and nuclear factor-kappa B (NF-κB) were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF), a well-known protective neurotrophin for retinal ganglion cells.     

Fe3O4/hydroxyapatite/graphene quantum dots as a novel nano-sorbent for preconcentration of copper residue in Thai food ingredients: Optimization of ultrasound-assisted magnetic solid phase extraction

Fe₃O₄/hydroxyapatite/graphene quantum dots (Fe₃O₄/HAP/GQDs) nanocomposite was synthesized and used as a novel magnetic adsorbent. This nanocomposite was characterized using scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and magnetization property. The Fe₃O₄/HAP/GQDs was applied to pre-concentrate copper residues in Thai food ingredients (so-called “Tom Yum Kung”) prior to determination by inductively coupled plasma-atomic emission spectrometry. Based on ultrasound-assisted extraction optimization, various parameters affecting the magnetic solid-phase extraction, such as solution pH, amount of magnetic nanoparticles, adsorption and desorption time, and type of elution solvent and its concentration were evaluated. Under optimal conditions, the linear range was 0.05–1500 ng mL⁻¹ (R² > 0.999), limit of detection was 0.58 ng mL⁻¹, and limit of quantification was 1.94 ng mL⁻¹. The precision, expressed as the relative standard deviation of the calibration curve slope (n = 5), for intra-day and inter-day analyses was 0.87% and 4.47%, respectively. The recovery study of Cu for real samples was ranged between 83.5% and 104.8%. This approach gave the enrichment factor of 39.2, which guarantees trace analysis of Cu residues. Therefore, Fe₃O₄/HAP/GQDs can be a potential and suitable candidate for the pre-concentration and separation of Cu from food samples. It can easily be reused after treatment with deionized water.     

ROS enhancement by silicon nanoparticles in X-ray irradiated aqueous suspensions and in glioma C6 cells

The capability of silicon nanoparticles to increase the yield of reactive species upon 4 MeV X-ray irradiation of aqueous suspensions and C6 glioma cell cultures was investigated. ROS generation was detected and quantified using several specific probes. The particles were characterized by FTIR, XPS, TEM, DLS, luminescence, and adsorption spectroscopy before and after irradiation to evaluate the effect of high energy radiation on their structure. The total concentration of O₂ ^•−/HO₂ ^•, HO^•, and H₂O₂ generated upon 4-MeV X-ray irradiation of 6.4 μM silicon nanoparticle aqueous suspensions were on the order of 10 μM per Gy, ten times higher than that obtained in similar experiments but in the absence of particles. Cytotoxic ¹O₂ was generated only in irradiation experiments containing the particles. The particle surface became oxidized to SiO₂ and the luminescence yield reduced with the irradiation dose. Changes in the surface morphology did not affect, within the experimental error, the yields of ROS generated per Gy. X-ray irradiation of glioma C6 cell cultures with incorporated silicon nanoparticles showed a marked production of ROS proportional to the radiation dose received. In the absence of nanoparticles, the cells showed no irradiation-enhanced ROS generation. The obtained results indicate that silicon nanoparticles of <5 nm size have the potential to be used as radiosensitizers for improving the outcomes of cancer radiotherapy. Their capability of producing ¹O₂ upon X-ray irradiation opens novel approaches in the design of therapy strategies.