Recent Advances in Copper-Based Organic Complexes and Nanoparticles for Tumor Theranostics.

Treatment of drug-resistant forms of cancer requires consideration of their hallmark features, such as abnormal cell death mechanisms or mutations in drug-responding molecular pathways. Malignant cells differ from their normal counterparts in numerous aspects, including copper metabolism. Intracellular copper levels are elevated in various cancer types, and this phenomenon could be employed for the development of novel oncotherapeutic approaches. Copper maintains the cell oxidation levels, regulates the protein activity and metabolism, and is involved in inflammation. Various copper-based compounds, such as nanoparticles or metal-based organic complexes, show specific activity against cancer cells according to preclinical studies. Herein, we summarize the major principles of copper metabolism in cancer cells and its potential in cancer theranostics.

Membrane-bound heat shock protein mHsp70 is required for migration and invasion of brain tumors.

Molecular chaperones, especially 70 kDa heat shock protein, in addition to their intracellular localization in cancer cells, can be exposed on the surface of the plasma membrane. We report that the membrane-associated chaperone mHsp70 of malignant brain tumors is required for high migratory and invasive activity of cancer cells. Live-cell inverted confocal microscopy of tumor samples from adult (n=23) and pediatric (n=9) neurooncological patients showed pronounced protein expression on the membrane, especially in the perifocal zone. Mass-spectrometry analysis of lipid rafts isolated from tumor cells confirmed the presence of the protein in chaperone cluster (including representatives of other families such as Hsp70, Hsc70, Hsp105, Hsp90), which in turn, during interactome analysis, was associated with proteins involved in cell migration (e.g., Rac1, RhoC, myosin-9). The use of small-molecule inhibitors of HSP70 (PES, JG-98) led to a significant decrease in the invasive potential of cells isolated from a tumor sample of patients, which indicates the role of the chaperone in invasion. Moreover, the use of HSP70 inhibitors in animal models of orthotopic brain tumors significantly delayed tumor progression, which was accompanied by an increase in overall survival. Data demonstrate that chaperone inhibitors, particularly JG-98, disrupt the function of mHsp70, thereby providing an opportunity to better understand the diverse functions of this protein and offer aid in the development of novel cancer therapies.

Nano- and Microemulsions in Biomedicine: From Theory to Practice.

Nano- and microemulsions are colloidal systems that are widely used in various fields of biomedicine, including wound and burn healing, cosmetology, the development of antibacterial and antiviral drugs, oncology, etc. The stability of these systems is governed by the balance of molecular interactions between nanodomains. Microemulsions as a colloidal form play a special important role in stability. The microemulsion is the thermodynamically stable phase from oil, water, surfactant and co-surfactant which forms the surface of drops with very small surface energy. The last phenomena determines the shortage time of all fluid dispersions including nanoemulsions and emulgels. This review examines the theory and main methods of obtaining nano- and microemulsions, particularly focusing on the structure of microemulsions and methods for emulsion analysis. Additionally, we have analyzed the main preclinical and clinical studies in the field of wound healing and the use of emulsions in cancer therapy, emphasizing the prospects for further developments in this area.

Magnetic Relaxation Switching Assay Using IFNα-2b-Conjugated Superparamagnetic Nanoparticles for Anti-Interferon Antibody Detection.

Type I interferons, particularly IFNα-2b, play essential roles in eliciting adaptive and innate immune responses, being implicated in the pathogenesis of various diseases, including cancer, and autoimmune and infectious diseases. Therefore, the development of a highly sensitive platform for analysis of either IFNα-2b or anti-IFNα-2b antibodies is of high importance to improve the diagnosis of various pathologies associated with the IFNα-2b disbalance. For evaluation of the anti-IFNα-2b antibody level, we have synthesized superparamagnetic iron oxide nanoparticles (SPIONs) coupled with the recombinant human IFNα-2b protein (SPIONs@IFNα-2b). Employing a magnetic relaxation switching assay (MRSw)-based nanosensor, we detected picomolar concentrations (0.36 pg/mL) of anti-INFα-2b antibodies. The high sensitivity of the real-time antibodies' detection was ensured by the specificity of immune responses and the maintenance of resonance conditions for water spins by choosing a high-frequency filling of short radio-frequency pulses of the generator. The formation of a complex of the SPIONs@IFNα-2b nanoparticles with the anti-INFα-2b antibodies led to a cascade process of the formation of nanoparticle clusters, which was further enhanced by exposure to a strong (7.1 T) homogenous magnetic field. Obtained magnetic conjugates exhibited high negative MR contrast-enhancing properties (as shown by NMR studies) that were also preserved when particles were administered in vivo. Thus, we observed a 1.2-fold decrease of the T2 relaxation time in the liver following administration of magnetic conjugates as compared to the control. In conclusion, the developed MRSw assay based on SPIONs@IFNα-2b nanoparticles represents an alternative immunological probe for the estimation of anti-IFNα-2b antibodies that could be further employed in clinical studies.

Mesenchymal Stem Cells and MSCs-Derived Extracellular Vesicles in Infectious Diseases: From Basic Research to Clinical Practice.

Mesenchymal stem cells (MSCs) are attractive in various fields of regenerative medicine due to their therapeutic potential and complex unique properties. Basic stem cell research and the global COVID-19 pandemic have given impetus to the development of cell therapy for infectious diseases. The aim of this review was to systematize scientific data on the applications of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) in the combined treatment of infectious diseases. Application of MSCs and MSC-EVs in the treatment of infectious diseases has immunomodulatory, anti-inflammatory, and antibacterial effects, and also promotes the restoration of the epithelium and stimulates tissue regeneration. The use of MSC-EVs is a promising cell-free treatment strategy that allows solving the problems associated with the safety of cell therapy and increasing its effectiveness. In this review, experimental data and clinical trials based on MSCs and MSC-EVs for the treatment of infectious diseases are presented. MSCs and MSC-EVs can be a promising tool for the treatment of various infectious diseases, particularly in combination with antiviral drugs. Employment of MSC-derived EVs represents a more promising strategy for cell-free treatment, demonstrating a high therapeutic potential in preclinical studies.

Biosensors and Drug Delivery in Oncotheranostics Using Inorganic Synthetic and Biogenic Magnetic Nanoparticles.

Magnetic nanocarriers have attracted attention in translational oncology due to their ability to be employed both for tumor diagnostics and therapy. This review summarizes data on applications of synthetic and biogenic magnetic nanoparticles (MNPs) in oncological theranostics and related areas. The basics of both types of MNPs including synthesis approaches, structure, and physicochemical properties are discussed. The properties of synthetic MNPs and biogenic MNPs are compared with regard to their antitumor therapeutic efficiency, diagnostic potential, biocompatibility, and cellular toxicity. The comparative analysis demonstrates that both synthetic and biogenic MNPs could be efficiently used for cancer theranostics, including biosensorics and drug delivery. At the same time, reduced toxicity of biogenic particles was noted, which makes them advantageous for in vivo applications, such as drug delivery, or MRI imaging of tumors. Adaptability to surface modification based on natural biochemical processes is also noted, as well as good compatibility with tumor cells and proliferation in them. Advances in the bionanotechnology field should lead to the implementation of MNPs in clinical trials.

Investigation of terahertz radiation influence on rat glial cells.

We studied an influence of continuous terahertz (THz) radiation (0.12 - 0.18 THz, average power density of 3.2 mW/cm2) on a rat glial cell line. A dose-dependent cytotoxic effect of THz radiation is demonstrated. After 1 minute of THz radiation exposure a relative number of apoptotic cells increased in 1.5 times, after 3 minutes it doubled. This result confirms the concept of biological hazard of intense THz radiation. Diagnostic applications of THz radiation can be restricted by the radiation power density and exposure time.