The structure, magnetic properties and ferromagnetic resonance curves of cobalt ferrite particles synthesized by chemical coprecipitation technique have been studied. The possibility of resonant heating of powder in a magnetic anisotropy field of particles is shown, which can find application in medicine for magnetic hyperthermia.
The need to develop a surgical instrument that can most effectively and minimally invasively remove a malignant tumor, and distinguish and destroy only tumor cells without damaging the normal cells of healthy tissue surrounding the tumor is being considered. To achieve this goal, it is proposed to use nanodiscs with special magnetic, electronic and optical properties. Nanodiscs modified with recognition ligands (aptamers) are able to bind to tumor cells and destroy them under the influence of a weak, nonheating alternating magnetic field. This allows for effective tumor destruction while minimizing the impact on surrounding healthy tissue.
By the example of α-Fe2O3 hematite, 5Fe2O3⋅9H2O ferrihydrite, and γ-Fe2O3 maghemite powders, a microwave-radiation-induced powder system temperature growth ΔTmax of several degrees has been measured in the ferromagnetic resonance mode at a frequency of 8.9 GHz. The powders heat up the most in the external field H coinciding with the ferromagnetic resonance field. The value of the ΔTmax effect depends on the magnetization of a powder material. The results obtained allow us to propose a new magnetic hyperthermia method for biomedical applications.
Gliomas remain challenging brain tumors to treat due to their infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful resection. This study introduces an innovative intraoperative visualization method utilizing surgical fluorescence microscopy to precisely locate tumor cell dissemination. Here, the focus is on the development of a novel contrasting agent (IR-Glint) for intraoperative visualization of human glial tumors comprising infrared-labeled Glint aptamers. The specificity of IR-Glint is assessed using flow cytometry and microscopy on primary cell cultures. In vivo effectiveness is studied on mouse and rabbit models, employing orthotopic xenotransplantation of human brain gliomas with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. The experiments validate the potential of IR-Glint for the intraoperative visualization of gliomas using infrared imaging. IR-Glint penetrates the blood-brain barrier and can be used for both intravenous and surface applications, allowing clear visualization of the tumor. The surface application directly to the brain reduces the dosage required and mitigates potential toxic effects on the patient. The research shows the potential of infrared dye-labeled aptamers for accurately visualizing glial tumors during brain surgery. This novel aptamer-assisted fluorescence-guided surgery (AptaFGS) may pave the way for future advancements in the field of neurosurgery.
Nickel and cobalt ferrite nanoparticles have been synthesized using the chemical precipitation method; the nanoparticle sizes were found to be 63 ± 22 and 26 ± 4 nm, respectively. The static hysteresis loops and Mössbauer spectra have been measured. It is shown that cobalt ferrite powders are magnetically harder than nickel ferrite powders. Ferromagnetic resonance (FMR) curves have been studied. It is found that the FMR absorption for cobalt ferrite is observed at room temperature and above. The time dependences of the nanoparticle warm-up under FMR conditions have been measured. The maximum temperature changes for nickel ferrite and cobalt ferrite particles are 8 and 11 K, respectively. Using the example of cobalt ferrite powder, the possibility of effectively heating of particles in the FMR mode in their own field without using a DC magnetic field source is shown. The observed effect can be used in magnetic hyperthermia.
Dental implant therapy is a well-accepted treatment modality. Despite good predictability and success in the early stages, the risk of postplacement inflammation in the long-term periods remains an urgent problem. Surgical access and decontamination with chemical and mechanical methods are more effective than antibiotic therapy. The search for the optimal and predictable way for peri-implantitis treatment remains relevant. Here, we evaluated four cleaning methods for their ability to preserve the implant's surface for adequate mesenchymal stem cell adhesion and differentiation. Implants isolated after peri-implantitis were subjected to cleaning with diamond bur; Ti-Ni alloy brush, air-flow, or Er,Cr:YSGG laser and cocultured with mice MSC for five weeks. Dental bur and titanium brushes destroyed the implants' surfaces and prevented MSC attachment. Air-flow and laser minimally affected the dental implant surface microroughness, which was initially designed for good cell adhesion and bone remodeling and to provide full microbial decontamination. Anodized with titanium dioxide and sandblasted with aluminum oxide, acid-etched implants appeared to be better for laser treatment. In implants sandblasted with aluminum oxide, an acid-etched surface better preserves its topology when treated with the air-flow. These cleaning methods minimally affect the implant's surface, so it maintains the capability to absorb osteogenic cells for further division and differentiation.
Nickel ferrite nanoparticles 4 nm in size were synthesized by chemical deposition. Subsequent annealing at T=700 o C for 5 h led to an increase in the particle size to 63 nm. The Mossbauer spectra and the frequency-field dependences of ferromagnetic resonance have been measured. It has been shown that freshly prepared powders are superparamagnetic at room temperature. The kinetic dependences of the heating of nanoparticles in the ferromagnetic resonance mode at a frequency of 8.9 GHz were measured. It was found that the maximum rate of temperature increase in this mode for a ferromagnetic powder is an order of magnitude greater than for the superparamagnetic state (1.2 and 0.13 K/s, respectively). The latter is determined by the saturation magnetization of the studied powders. Keywords: ferromagnetic resonance, superparamagnetic powders, relaxation frequency, frequency-field dependence, heating of powders.
Here, we present DNA aptamers capable of specific binding to glial tumor cells in vitro, ex vivo, and in vivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ, ex vivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show in vivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors.
Magnetic nanoparticles of magnetite with a size of ~8 nm synthesized with a different type of coating were studied by ferromagnetic resonance in the temperature range from 7 to 300 K. The features of the experimental temperature dependences of the parameters of the ferromagnetic resonance curve (the magnitude of the resonant field, line width and intensity) and their approximation allowed us to estimate the values of characteristic temperatures. Firstly, the value of the Vervey temperature and the dependence of its value on the type of coating were determined. Secondly, the temperature of transition of nanoparticles to the superparamagnetic state (blocking temperature) and the temperature range within which the magnetic structure of the outer shell of the magnetic nanoparticle is in the spin glass state are established Keywords: iron oxide nanoparticles, ferromagnetic resonance, superparamagnetism, blocking temperature.
Magnetic nanoparticles of magnetite with a size of ~8 nm synthesized with a different type of coating were studied by ferromagnetic resonance in the temperature range from 7 to 300 K. The features of the experimental temperature dependences of the parameters of the ferromagnetic resonance curve (the magnitude of the resonant field, line width and intensity) and their approximation allowed us to estimate the values of characteristic temperatures. Firstly, the value of the Vervey temperature and the dependence of its value on the type of coating were determined. Secondly, the temperature of transition of nanoparticles to the superparamagnetic state (blocking temperature) and the temperature range within which the magnetic structure of the outer shell of the magnetic nanoparticle is in the spin glass state are established
Nickel ferrite nanoparticles 4 nm in size were synthesized by chemical deposition. Subsequent annealing at T=700℃ for 5 h led to an increase in the particle size to 63 nm. The Mössbauer spectra and the frequency-field dependences of ferromagnetic resonance have been measured. It has been shown that freshly prepared powders are superparamagnetic at room temperature. The kinetic dependences of the heating of nanoparticles in the ferromagnetic resonance mode at a frequency of 8.9 GHz were measured. It was found that the maximum rate of temperature increase in this mode for a ferromagnetic powder is an order of magnitude greater than for the superparamagnetic state (1.2 and 0.13 K/s, respectively). The latter is determined by the saturation magnetization of the studied powders.
One of the promising novel methods for radical tumor resection at a single-cell level is magneto-mechanical microsurgery (MMM) with magnetic nano- or microdisks modified with cancer-recognizing molecules. A low-frequency alternating magnetic field (AMF) remotely drives and controls the procedure. Here, we present characterization and application of magnetic nanodisks (MNDs) as a surgical instrument ("smart nanoscalpel") at a single-cell level. MNDs with a quasi-dipole three-layer structure (Au/Ni/Au) and DNA aptamer AS42 (AS42-MNDs) on the surface converted magnetic moment into mechanical and destroyed tumor cells. The effectiveness of MMM was analyzed on Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo using sine and square-shaped AMF with frequencies from 1 to 50 Hz with 0.1 to 1 duty-cycle parameters. MMM with the "Nanoscalpel" in a sine-shaped 20 Hz AMF, a rectangular-shaped 10 Hz AMF, and a 0.5 duty cycle was the most effective. A sine-shaped field caused apoptosis, whereas a rectangular-shaped field caused necrosis. Four sessions of MMM with AS42-MNDs significantly reduced the number of cells in the tumor. In contrast, ascites tumors continued to grow in groups of mice and mice treated with MNDs with nonspecific oligonucleotide NO-MND. Thus, applying a "smart nanoscalpel" is practical for the microsurgery of malignant neoplasms.
Powders of maghemite γ-Fe 2 O 3 with an average diameter of 8 nm, γ-Fe 2 O 3 /SiO 2 composites with an agglomerate diameter of about 50 nm and a size of interspersed γ-Fe 2 O 3 particles of 6 nm, and γ‑Fe 2 O 3 /SiO 2 /aptamer(FAS9) composites were synthesized by chemical deposition. Mössbauer spectra were measured, the static and dynamic magnetic properties of the powders were studied, and the coercive force was determined, which decreases from 14 Oe for γ-Fe 2 O 3 powders to 3 Oe for the γ-Fe 2 O 3 /SiO 2 composite. It is shown that the particle blocking temperature is close to room temperature. The increment of temperature of the powders was measured in the ferromagnetic resonance mode; the temperature of the Fe 2 O 3 /SiO 2 composite (Δ T ≈ 16°C) turned out to be higher than that of the pure γ-Fe 2 O 3 powder (Δ T ≈ 10°C). It has been experimentally shown that temperature increment Δ T is proportional to the square of the microwave field amplitude. It has been shown that the composition γ-Fe 2 O 3 /SiO 2 /aptamer FAS9 is able to effectively bind to tumor cells, and FMR hyperthermia leads to a decrease in the viability of tumor cells.
Cisplatin is an effective drug for treating various cancer types. However, it is highly toxic for both healthy and tumor cells. Therefore, there is a need to reduce its therapeutic dose and increase targeted bioavailability. One of the ways to achieve this could be the coating of cisplatin with polysaccharides and specific carriers for targeted delivery. Nucleic acid aptamers could be used as carriers for the specific delivery of medicine to cancer cells. Cisplatin-arabinogalactan-aptamer (Cis-AG-Ap) conjugate was synthesized based on Cis-dichlorodiammineplatinum, Siberian larch arabinogalactan, and aptamer AS-42 specific to heat-shock proteins (HSP) 71 kDa (Hspa8) and HSP 90-beta (Hsp90ab1). The antitumor effect was estimated using ascites and metastatic Ehrlich tumor models. Cis-AG-Ap toxicity was assessed by blood biochemistry on healthy mice. Here, we demonstrated enhanced anticancer activity of Cis-AG-Ap and its specific accumulation in tumor foci. It was shown that targeted delivery allowed a 15-fold reduction in the therapeutic dose of cisplatin and its toxicity. Cis-AG-Ap sufficiently suppressed the growth of Ehrlich's ascites carcinoma, the mass and extent of tumor metastasis in vivo. Arabinogalactan and the aptamers promoted cisplatin efficiency by enhancing its bioavailability. The described strategy could be very promising for targeted anticancer therapy.
Films from biodegradable poly-3-hydroxybutyrate are treated with chemical reagents to improve their hydrophilicity and biocompatibility. Two approaches are tested: a single treatment with alkali, acids, oxidizing or reducing agents, and a step-by step treatment of the alkali pre-activated surface of polymer films with bromine water and amino-compounds (ammonia or triethylamine). The maximal level of hydrophilicity (the lowest water contact angle and the highest polar component of the surface free energy) is registered after a single treatment with NaOH and after the step-by-step treatment. These samples also showed the best adhesion of mouse fibroblasts of NIH 3T3 line on the film surface. So, the proposed methods can be used to enhance hydropilicity and biocompatibility of biopolymer surface.
A series of films was obtained from blends of poly-3-hydroxybutyrate (PHB) and poly-s-caprolactone (PCL). The structure, physical, mechanical and biological properties of the films were studied, depending on the ratio of the components. The microscopic structure of mixed films was determined by the main component of the blend: the films were porous with a predominance of PHB and relatively smooth with a predominance of PCL. The highest values of elongation at break (229-269%), as well as the local maximum values of tensile strength (14-15 MPa) were noted for blends with 5-25% PHB content. At PHB content of 25% and 75%, local maxima of Young’s modulus were observed (507 and 655 MPa, respectively). When the ratio of the components in the blend was equal (50:50 by weight), the films were heterogeneous and had the lowest values of mechanical strength (ultimate strength and elongation at break were 3 MPa and 15.5%, respectively). A study of the biocompatibility of mixed films in a culture of NIH 3T3 mouse fibroblasts based on determination of the number of adhered cells in the MTT test showed the absence of cytotoxic action, as well as high adhesion and cell proliferation, in some cases exceeding the data for films from pure PHB and PCL. This demonstrates the suitability of PHB-PCL blends for the production of cell carriers for tissue engineering and other reconstructive technologies.
Так называемое «немецкое засилье» в России в годы Первой мировой войны вызвало широкий общественный резонанс и послужило основанием для правовых ограничений всех подданных воюющих с Россией государств. В статье рассматриваются причины этого явления, вызванного не только вполне естественным отрицательным отношением к врагу, противостоявшему российской армии, но и попытками создать своеобразное единство в сфере этнических отношений. Результатом явилось появление наряду с беженцами «вынужденных мигрантов», ряды которых состояли в том числе и из российских подданных немецкого и австрийского происхождения, многие десятилетия проживавших на территории России. Российская власть в какой-то мере оценивала возможные экономические последствия подобных мер, принявших массовый характер, но, находясь под постоянным давлением со стороны общества и армейского командования, вынуждена была предпринять шаги по введению ограничительных законов в отношении «внутренних врагов».
Vemurafenib revolutionized the treatment of melanomas which harbor mutations in BRAF oncogene whereas BRAF -negative tumors are resistant to its antitumor effects. Meanwhile tumor chemoresistance is associated with the presence of quiescent, resting-dormant (G 0 -positive, Ki-67-negative) cancer cells in the heterogeneous cancer cell population. In order to test if BRAF-inhibitor can stimulate quiescence in melanoma cells, two melanoma cell lines (BRO and SK-MEL-2) were treated with the antitumor drug vemurafenib, and populations with G 1 /G 0 cell cycle arrest were obtained. The latter were confirmed by negative staining with Ki-67 antibodies, and changes in the gene expression of cell cycle regulatory proteins, such as CDK4 , CCND1 and CDKN1B .
MicroRNAs epigenetically regulate physiological and pathological processes. Previously, we found that miR-204-5p is expressed at low levels in melanoma cells, and an increase in its level leads to a change in proliferation, migration, and invasion of these cancer cells. Now, using bioinformatics analysis, it has been shown that the target of miR-204-5p is FOXC1 transcription factor, which is implicated in carcinogenesis. Using the luciferase reporter assay, it was found that miR-204-5p suppresses expression of the FOXC1 gene by binding to its 3' non-coding region. Transfection of small interfering RNA (siRNA) targeting FOXC1 into melanoma cells caused a decrease in miR-204-5p levels, which is consistent with the generally accepted concept of feedback regulation of miRNA expression by target genes. According to the results of the MTT test and fluorescence microscopy, the proliferation level of melanoma cells under the influence of siRNA to FOXC1 decreased 72 h after transfection. Changes in the ratio of cells by cell cycle phase were analyzed using flow cytometry. Regulatory relationships between FOXC1 and miR-204-5p, and an inhibitory effect of FOXC1 knockdown on melanoma cell proliferation were revealed. Based on the results, it can be assumed that miR-204-5p regulates proliferation of melanoma cells by affecting FOXC1 expression.