Extracellular vesicles (EVs) show great potential for therapeutic delivery to human cells, with a focus on modulating immune responses. The most promising targets for inducing humoral and cellular immunity against a specific antigen are macrophages (Mϕs) and dendritic cells (DCs). Targeting mannose receptors (CD206), which are highly expressed on these antigen-presenting cells, to promote the presentation of specific antigens through EV-mediated uptake, is a promising strategy in clinical immunotherapy.
View Article and Find Full Text PDFBackground: Detailed characterization of extracellular vesicles (EVs) is crucial for their application in medical diagnostics. However, the complexity of their chemical composition and the heterogeneity of EV populations make their characterization challenging. Here we describe two analytical procedures that can help overcome this challenge.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are of growing interest in the context of screening for highly informative cancer markers. We have previously shown that uterine aspirate EVs (UA EVs) are a promising source of ovarian cancer (OC) diagnostic markers. In this study, we first conducted an integrative analysis of EV-miRNA profiles from UA, malignant ascitic fluid (AF), and a conditioned medium of cultured ascites cells (ACs).
View Article and Find Full Text PDFProteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of cancer, primarily in solid tumors, is limited due to poor pharmacokinetics, inefficient tissue penetration, low stability and frequent adverse effects. In the present study, a novel micellar nano-scaled delivery system was manufactured, composed of amphiphilic poly(N-vinylpyrrolidone) nanoparticles loaded with bortezomib.
View Article and Find Full Text PDFCurcumin attracts huge attention because of its biological properties: it is antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems, we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone).
View Article and Find Full Text PDFBackground: Activity-regulated cytoskeleton-associated (Arc) protein is predominantly expressed in excitatory glutamatergic neurons of vertebrates, where it plays a pivotal role in regulation of synaptic plasticity. Arc protein forms capsid-like particles, which can encapsulate and transfer mRNA in extracellular vesicles (EVs) between hippocampal neurons. Once glioma cell networks actively interact with neurons via paracrine signaling and formation of neurogliomal glutamatergic synapses, we predicted the involvement of Arc in a process of EV-mediated mRNA transfer between glioma cells.
View Article and Find Full Text PDFSo far, only a few articles have demonstrated the possibility of correlated AFM-TEM imaging - sequential imaging of the same individual objects using atomic-force microscopy (AFM) and transmission electron microscopy (TEM). The current work contributes to the development of this approach by giving a step-by-step procedure, which yields pairs of correlated AFM-TEM images. We describe the application of correlation AFM-TEM microscopy to lipid nanoparticles (small extracellular vesicles and liposomes).
View Article and Find Full Text PDFBiocompatible polyesters are widely used in biomedical applications, including sutures, orthopedic devices, drug delivery systems, and tissue engineering scaffolds. Blending polyesters with proteins is a common method of tuning biomaterial properties. Usually, it improves hydrophilicity, enhances cell adhesion, and accelerates biodegradation.
View Article and Find Full Text PDFSecreted extracellular vesicles (EVs) contain active biomolecules, including miRNAs, composition of which reflects epigenetic changes occurring in cells during pathological processes, in particular, malignant transformation. The accumulated pool of data on the role of EVs in carcinogenesis has stimulated investigations of the EV-derived cancer markers. The most important factor limiting development of this scientific direction is lack of "gold standards" both for methods of EV isolation from biological fluids and for analyzing their molecular content, including composition of miRNAs.
View Article and Find Full Text PDFApplication of nanocarriers for drug delivery brings numerous advantages, allowing both minimization of side effects common in systemic drug delivery and improvement in targeting, which has made it the focal point of nanoscience for a number of years. While most of the studies are focused on encapsulation of hydrophobic drugs, delivery of hydrophilic compounds is typically performed via covalent attachment, which often requires chemical modification of the drug and limits the release kinetics. In this paper, we report synthesis of biphilic copolymers of various compositions capable of self-assembly in water with the formation of nanoparticles and suitable for ionic binding of the common anticancer drug doxorubicin.
View Article and Find Full Text PDFTick-borne encephalitis virus (TBEV) is an enveloped RNA virus, a member of the genus (family ). Here, we provide a detailed analysis of the size and structure of the inactivated TBEV vaccine strain Sofjin-Chumakov. Four analytical methods were used to analyze individual TBEV particles-negative staining TEM, cryo-EM, atomic force microscopy (AFM), and nanoparticle tracking analysis (NTA).
View Article and Find Full Text PDFModification of the cell surface with artificial nano- and microparticles (also termed "cellular backpacks") containing biologically active payloads usually enables drug targeting via harnessing intrinsic cell tropism to the sites of injury. In some cases, using cells as delivery vehicles leads to improved pharmacokinetics due to extended circulation time of cell-immobilized formulations. Another rationale for particle attachment to cells is augmentation of desirable cellular functions and cell proliferation in response to release of the particle contents.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are promising agents for liquid biopsy-a non-invasive approach for the diagnosis of cancer and evaluation of therapy response. However, EV potential is limited by the lack of sufficiently sensitive, time-, and cost-efficient methods for their registration. This research aimed at developing a highly sensitive and easy-to-use immunochromatographic tool based on magnetic nanoparticles for EV quantification.
View Article and Find Full Text PDFWetting of electrospun mats plays a huge role in tissue engineering and filtration applications. However, it is challenging to trace the interrelation between the wetting of individual nano-sized fibers and the macroscopic electrospun mat. Here we measured the wetting of different nylon-11 samples - solution-cast films, electrospun fibers deposited onto a substrate, and free-standing mats.
View Article and Find Full Text PDFExtracellular vesicles (EVs), including exosomes, are key factors of intercellular communication, performing both local and distant transfers of bioactive molecules. The increasingly obvious role of EVs in carcinogenesis, similarity of molecular signatures with parental cells, precise selection and high stability of cargo molecules make exosomes a promising source of liquid biopsy markers for cancer diagnosis. The uterine cavity fluid, unlike blood, urine and other body fluids commonly used to study EVs, is of local origin and therefore enriched in EVs secreted by cells of the female reproductive tract.
View Article and Find Full Text PDFDevelopment of CAR-T therapy led to immediate success in the treatment of B cell leukemia. Manufacturing of therapy-competent functional CAR-T cells needs robust protocols for ex vivo/in vitro expansion of modified T-cells. This step is challenging, especially if non-viral low-efficiency delivery protocols are used to generate CAR-T cells.
View Article and Find Full Text PDFNanoparticles based on the biocompatible amphiphilic poly(-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with the formation of micellar nanoscaled structures. Amph-PVP nanoparticles are able to immobilize therapeutic molecules under mild conditions.
View Article and Find Full Text PDFThe severe COVID-19 pandemic drives the research toward the SARS-CoV-2 virion structure and the possible therapies against it. Here, we characterized the β-propiolactone inactivated SARS-CoV-2 virions using transmission electron microscopy (TEM) and atomic force microscopy (AFM). We compared the SARS-CoV-2 samples purified by two consecutive chromatographic procedures (size exclusion chromatography [SEC], followed by ion-exchange chromatography [IEC]) with samples purified by ultracentrifugation.
View Article and Find Full Text PDFDelivering protein therapeutics specifically into target cells and tissues is a promising avenue in medicine. Advancing this process will significantly enhance the efficiency of the designed drugs. In this regard, natural membrane-based systems are of particular interest.
View Article and Find Full Text PDFThe morphology and proliferation of eukaryotic cells depend on their microenvironment. When electrospun mats are used as tissue engineering scaffolds, the local alignment of the fibers has a pronounced influence on cells. Here we analyzed the morphology of the patterned mats produced by electrospinning of PLA-gelatin blend onto a conductive grid.
View Article and Find Full Text PDFExosomes are the small vesicles that are secreted by different types of normal and tumour cells and can incorporate and transfer their cargo to the recipient cells. The main goal of the present work was to study the tumour exosomes' ability to accumulate the parent mutant DNA or RNA transcripts with their following transfer to the surrounding cells. The experiments were performed on the MCF7 breast cancer cells that are characterized by the unique coding mutation in the gene.
View Article and Find Full Text PDFTransmission electron microscopy (TEM) is the most widely accepted method for visualization of extracellular vesicles (EVs), and particularly, exosomes. TEM images provide us with information about the size and morphology of the EVs. We have developed an online tool ScanEV (Scanner for the Extracellular Vesicles, available at https://bioeng.
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