Glial tumors, particularly glioblastomas, remain among the most challenging cancers to diagnose and treat due to their heterogeneity, infiltrative nature, and the protective blood-brain barrier that impedes drug delivery. Aptamers-short, single-stranded nucleic acids selected for high-affinity target binding-have emerged as promising agents in neuro-oncology, offering advantages such as high specificity, low immunogenicity, and superior tissue penetration compared to conventional antibodies. This review outlines recent advancements in aptamer-based technologies for the diagnosis and treatment of glial brain tumors. We describe the use of aptamers in molecular imaging, liquid biopsy platforms, intraoperative tumor visualization, and the targeted delivery of therapeutic agents, including small molecules, small interfering RNAs (siRNAs), and immunomodulators. The integration of aptamer systems with nanotechnology and AI is accelerating the development of sensitive, non-invasive diagnostic tools and multifunctional theranostic platforms.

BACKGROUND:With the rising incidence of cancer, there is a growing need for improved preclinical models to test new therapies. While patient-derived xenografts (PDX) in immunodeficient mice are the gold standard, they are costly and result in a complete absence of a functional immune system, limiting their utility for studying tumor-immune interactions. This study characterizes a pharmacological partial immunosuppression protocol in immunocompetent mice as a promising alternative, evaluating its impact on the immune system and demonstrating its efficacy for growing human tumor xenografts. METHODS:Mice received a regimen of cyclosporine (20 mg/kg, i.p., every 48 h for 12 days), cyclophosphamide (60 mg/kg, i.p., every 48 h for 8 days), and ketoconazole (10 mg/kg, p.o., for 12 days). The dynamics of CD3+, CD4+, CD8+, and CD19+ lymphocyte subpopulations and the CD4/CD8 index were monitored via flow cytometry on days 1, 5, 8, 12, 16, and 21. The protocol's utility was tested by orthotopic transplantation of human glioma and lung cancer cells, and subcutaneous transplantation of breast cancer cells (MCF7). Tumor engraftment and growth were assessed using in vivo microscopy, MRI, and histology. RESULTS:The immunosuppressive protocol induced a significant but partial reduction in CD3+ T-cells and CD19+ B-cells by day 8 (p = 0.0277). A profound and progressive decrease in the CD4/CD8 index was observed, indicating a shift towards immunosuppression. Crucially, CD8+ and CD4+ T-cells populations recovered rapidly post-therapy, demonstrating that the protocol creates a temporary and modifiable immune window rather than inducing complete ablation. The protocol enabled successful engraftment and growth of all three tested tumors in a residual immune microenvironment, confirmed by in vivo imaging and histopathological analysis. CONCLUSIONS:This drug-induced partial immunosuppression protocol effectively creates a reproducible state of transient immunodeficiency in outbred mice, suitable for various human tumor xenograft models. It represents a cost-effective and flexible alternative to genetic models, with the distinct advantage of preserving a residual immune microenvironment, making it particularly valuable for preclinical studies that require a partially intact host immune system.

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.

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.

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.

Purpose of the study : to evaluate the feasibility of using functional analogues of protein antibodies – dNa/ RNa aptamers in diagnostics, treatment and prognosis of human brain glial tumors. Material and Methods . The relevant literature sources were searched in scopus, Web of science, pubmed, elibrary with inclusion of publications from 2000 to 2023. sixty articles are presented in the review. Results. The analysis of the literature devoted to classification, diagnostics and therapy of brain glioblastomas was carried out and the feasibility of using for in vivo diagnostics and therapy of this disease aptamers, which are molecular recognition elements based on DNA/RNA oligonucleotides, capable of binding to the given molecular targets and distinguishing even separate functional groups in them, was studied. A list of aptamers to human glial brain tumors and their molecular targets that can be used for diagnostics and therapy of glioblastoma, including tumor imaging by pet/ct, mRi, plasmon resonance, fluorescence and confocal microscopy, etc., is presented. literature data suggest that DNA/RNA aptamers can be used to search for circulating tumor cells in the blood of glioblastoma patients, to target therapeutic drugs to the tumor and to inhibit tumor growth. Conclusion. Brain glioblastoma is a heterogeneous tumor consisting of cells at different stages of malignancy and, accordingly, with a different set of oncogenes. For this reason, a multitarget strategy that includes combined suppression of angiogenesis, invasion, metastasis, proliferation and survival of tumor cells should be proposed for the therapy of this disease. DNA/RNA aptamers tailored to key proteins involved in oncogenic transformation may be suitable candidates for the implementation of multitarget therapy for brain glioblastoma.

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.

Patients with drug-resistant epilepsy (DRE) due to an arteriovenous malformation (AVM) located in a functionally significant area of the brain experience a significant decrease in quality of life and require additional non-drug rehabilitation methods aimed at controlling epileptic symptoms. Aim. To present a clinical observation of the use of the Epi-Tapp (R) application in a 29-year-old patient with an AVM. Materials and methods. We used the author's wrist tapping method EpiTapp (R) (RF patent No. 2606489 dated January 10, 2017). Results. Using the EpiTapp (R) application allowed a 29-year-old man with an AVM to reduce the severity and duration of focal seizures in 85% of cases and prevent secondary bilateral transformation of incipient bilateral tonic-clonic seizures in more than 50% of cases. Conclusions. This clinical case demonstrates the possibility of effectively using the EpiTapp (R) application in a patient with drug-resistant epilepsy as an element of a rehabilitation program aimed at controlling epileptic seizures.

Magnetomechanical therapy is one of the most perspective directions in tumor microsurgery. According to the analysis of recent publications, it can be concluded that a nanoscalpel could become an instrument sufficient for cancer microsurgery. It should possess the following properties: (1) nano- or microsized; (2) affinity and specificity to the targets on tumor cells; (3) remote control. This nano- or microscalpel should include at least two components: (1) a physical nanostructure (particle, disc, plates) with the ability to transform the magnetic moment to mechanical torque; (2) a ligand—a molecule (antibody, aptamer, etc.) allowing the scalpel precisely target tumor cells. Literature analysis revealed that the most suitable nanoscalpel structures are anisotropic, magnetic micro- or nanodiscs with high-saturation magnetization and the absence of remanence, facilitating scalpel remote control via the magnetic field. Additionally, anisotropy enhances the transmigration of the discs to the tumor. To date, four types of magnetic microdiscs have been used for tumor destruction: synthetic antiferromagnetic P-SAF (perpendicular) and SAF (in-plane), vortex Py, and three-layer non-magnetic–ferromagnet–non-magnetic systems with flat quasi-dipole magnetic structures. In the current review, we discuss the biological effects of magnetic discs, the mechanisms of action, and the toxicity in alternating or rotating magnetic fields in vitro and in vivo. Based on the experimental data presented in the literature, we conclude that the targeted and remotely controlled magnetic field nanoscalpel is an effective and safe instrument for cancer therapy or theranostics.

Nanotechnologies involving physical methods of tumor destruction using functional oligonucleotides are promising for targeted cancer therapy. Our study presents magnetodynamic therapy for selective elimination of tumor cells in vivo using DNA aptamer-functionalized magnetic nanoparticles exposed to a low frequency alternating magnetic field. We developed an enhanced targeting approach of cancer cells with aptamers and arabinogalactan. Aptamers to fibronectin (AS-14) and heat shock cognate 71 kDa protein (AS-42) facilitated the delivery of the nanoparticles to Ehrlich carcinoma cells, and arabinogalactan (AG) promoted internalization through asialoglycoprotein receptors. Specific delivery of the aptamer-modified FeAG nanoparticles to the tumor site was confirmed by magnetic resonance imaging (MRI). After the following treatment with a low frequency alternating magnetic field, AS-FeAG caused cancer cell death in vitro and tumor reduction in vivo. Histological analyses showed mechanical disruption of tumor tissues, total necrosis, cell lysis, and disruption of the extracellular matrix. The enhanced targeted magnetic theranostics with the aptamer conjugated superparamagnetic ferroarabinogalactans opens up a new venue for making biocompatible contrasting agents for MRI imaging and performing non-invasive anti-cancer therapies with a deep penetrated magnetic field.

This review examines the epidemiology of drug resistant epilepsy in adults in Russia and abroad. References were taken from Russian and foreign databases for the period from 2010–2017. Only full-text publications (66) were included in this review. We concluded that the despite the achievements of clinical pharmacology and the development of new antiepileptic drugs, the problem of drug resistant epilepsy remains not fully resolved today. The worldwide high prevalence rate of patients with drug resistant epilepsy substantiates the problem. Thus, the average incidence of this disease varies from 30% to 70%, depending on the type of epilepsy and background pathology, which is the cause of symptomatic epilepsy. However, we have faced the problem of the absence both in Russia and abroad of large multicenter studies on the epidemiology of drug resistant epilepsy in the analyzed period of time. We have also revealed the lack of a unified definition of the disease, which is probably one of the reasons for the insufficient number of epidemiological studies of drug resistant epilepsy in different countries of the world.

The review is dedicated to the problems of current neurosurgical treatment for drug-resistant epilepsy in the adult population of Russia and foreign countries. The literature published in the period 2010–2017 was sought in Russian and foreign databases. This review included 58 only full-text publications. The search results have shown that despite advances in neurosurgery for drug-resistant epilepsy and the development of new surgical procedures, the problem of this disease has not yet been fully resolved today. This is evidenced by fairly high global prevalence rates in patients with postoperative epilepsy resistant to antiepileptic therapy. The literature analysis has revealed that the mean prevalence of postoperative epilepsy is 69%. This indicator may vary according to the type of an epileptogenic structural lesion and its location in the brain. However, despite the rapid development of epilepsy surgery, currently there is still a low surgical activity in the treatment of patients with drugresistant epilepsy. Of importance is also the presence of postoperative complications, including various infectious complications and neurological deficit. Taking into account the high rate of postoperative epilepsy, it is concluded that it is appropriate to develop postoperative rehabilitation methods for patients with drug-resistant epilepsy.

The aim of the present study was to assess the main characteristics of the tempo-rhythm in healthy adults. Materials and Methods: We examined 60 healthy adults without neurological and endocrinological pathology. Participants were divided into 2 groups. In Group 1 there were 33 adults without deviations on the scale of anxiety and depression were, and in Group 2, there were 27 persons with subclinically expressed anxiety according to the test results. The test was conducted using hospital anxiety and depression scale HADS. The study was conducted using a modified original technique "Method of exogenous rhythmic stimulation influence on an individual human rhythm." Results: We found that anxiety statistically significant affects the quantitative and qualitative parameters of wrist tapping (individual rhythm and rhythm stability) in healthy adults. Conclusion: The obtained data can be used in neurorehabilitation for adult patients with a wide range of neurological disorders, including epilepsy.

The review focuses on the problem of personality disorders that arise in patients with pharmaco-resistant epilepsy after neurosurgical resections. We analyzed 47 research articles, selected by keywords from Russian and international databases for 20102017. It was found that, despite the achievements in epilepsy surgery and the high percentage of remission in the postoperative period, the problem of personality disorders remains important. The most frequent postoperative personality disorders are anxiety and depression, which greatly exacerbate the course of the postoperative period and make it difficult for the patient to adapt in society because of his internal stigmatization. In addition, depression can provoke the aggravation of epileptic seizures in the postoperative period. Psychiatric anamnesis and a severe form of depression in the preoperative period are the powerful predictors of the depression onset in the postoperative period. Despite this, there are no psychiatric contraindications to the surgical treatment of pharmaco-resistant epilepsy. The authors discuss the need for perioperative psychiatric testing of patients suffering from epilepsy.

Красноярский государственный медицинский университет имени профессора В

Here we describe a method of forming large arrays (up to 109 pieces) of free magnetic Ni-nanodisks 50 nm thick coated on both sides with layers of 5 nm thick Au. The antitumor effect of the magnetic nickel gold-coated nanodisks and DNA aptamer conjugates was evaluated in vivo and in vitro. Under the influence of rotating magnetic field, the studied nanodisks can cause the death of Ehrlich ascites carcinoma cells.