For the first time, by using the complex of physicochemical methods (mass-spectrometry, differential scanning calorimetry, spectrofluorimetry, method of spectral and fluorescent probes, dynamic light scattering, and UV spectrophotometry), the oxidation-mediated modification of chemical and spatial structure of albumin has been studied. All albumin structural regions are subjected to oxidation, methionine and aromatic amino acids primarily involved in oxidation. The albumin melting shows a decrease in thermal stabilization of the structure and changing of aggregation upon oxidation. The change in physical and chemical properties of albumin under different quantity of the oxidizer has been analyzed.

Magnetic nanosystems (MNSs) consisting of magnetic iron oxide nanoparticles (IONPs) coated by human serum albumin (HSA), commonly used as a component of hybrid nanosystems for theranostics, were engineered and characterized. The HSA coating was obtained by means of adsorption and free radical modification of the protein molecules on the surface of IONPs exhibiting peroxidase-like activity. The generation of hydroxyl radicals in the reaction of IONPs with hydrogen peroxide was proven by the spin trap technique. The methods of dynamic light scattering (DLS) and electron magnetic resonance (EMR) were applied to confirm the stability of the coatings formed on the surface of the IONPs. The synthesized MNSs (d ~35 nm by DLS) were intraarterially administered in tumors implanted to rats in the dose range from 20 to 60 μg per animal and studied in vivo as a contrasting agent for computed tomography. The long-term (within 14 days of the experiment) presence of the MNSs in the tumor vascular bed was detected without immediate or delayed adverse reactions and significant systemic toxic effects during the observation period. The peroxidase-like activity of MNSs was proven by the colorimetric test with o-phenylenediamine (OPD) as a substrate. The potential of the synthesized MNSs to be used for theranostics, particularly, in oncology, was discussed.

The generation of hydroxyl radicals from hydrogen peroxide in aqueous solutions containing magnetic nanoparticles (MNPs), hemoglobin (Hb), immunoglobulin G (IgG), and human serum albumin (HSA) was determined. The dependence of the rate of formation of the oxidized product of o-phenylenediamine (o-PDA) on the concentration of MNPs in solution, as well as on the concentration of proteins, was obtained. The peroxidase-like activity of MNPs was shown to decrease in the presence of HSA and IgG, while the addition of Hb to the reaction mixture led to its decrease and increase depending on protein concentration. The obtained effects can be used in the engineering of systems based on MNPs for theranostics (in particular, for suppression of tumor growth) and in predicting the ability of particles to catalyze the generation of reactive oxygen species (ROS) in vivo.

Background/Objectives: Magnetic iron oxide nanoparticles (IONPs), human serum albumin (HSA) and folic acid (FA) are prospective components for hybrid nanosystems for various biomedical applications. The magnetic nanosystems FA-HSA@IONPs (FAMs) containing IONPs, HSA, and FA residue are engineered in the study. Methods: Composition, stability and integrity of the coating, and peroxidase-like activity of FAMs are characterized using UV/Vis spectrophotometry (colorimetric test using o-phenylenediamine (OPD), Bradford protein assay, etc.), spectrofluorimetry, dynamic light scattering (DLS) and electron magnetic resonance (EMR). The selectivity of the FAMs accumulation in cancer cells is analyzed using flow cytometry and confocal laser scanning microscopy. Results: FAMs (d_N~55 nm by DLS) as a drug delivery platform have been administered to cancer cells (human breast adenocarcinoma MCF-7 and MDA-MB-231 cell lines) in vitro. Methylene blue, as a model photosensitizer, has been non-covalently bound to FAMs. An increase in photoinduced cytotoxicity has been found upon excitation of the photosensitizer bound to the coating of FAMs compared to the single photosensitizer at equivalent concentrations. The suitability of the nanosystems for photodynamic therapy has been confirmed. Conclusions: FAMs are able to effectively enter cells with increased folate receptor expression and thus allow antitumor photosensitizers to be delivered to cells without any loss of their in vitro photodynamic efficiency. Therapeutic and diagnostic applications of FAMs in oncology are discussed.

For the first time, with the aid of differential scanning calorimetry, the thermal denaturation of fibrinogen under induced oxidation was studied. All fibrinogen structural elements detected by DSC...

Folic acid (FA) residue is a well-known and widely spread targeting ligand, or biovector, used as a component in engineering artificial nanosized and submicron particles (NSPs) to target various cells and treat a variety of diseases that are associated with FA (or folate) receptors (FR) overexpression. A particular place in the list of these diseases is held by various cancer types, for which overexpression of FR on the cell surface is often accompanied by a more severe disease course, increased resistance to the conventional chemotherapy, and poorer prognosis. The incorporation of albumin into NSPs has been shown to enhance their biocompatibility, give high compatibility with drug molecules, prolong their circulation, reduce thrombogenic activity, and improve their colloidal stability. Nowadays albumin-based NSPs with FA residue as a targeting agent are used for chemotherapy, photothermal and photodynamic therapy, combined therapy, visualization, and theranostics (also known as theragnostics) for various types of cancer: breast, cervical, ovarian, prostate, nasopharyngeal, gastric, colorectal, liver cancer, and brain tumors. A limited number of studies have also focused on the use of NSPs in rheumatoid arthritis treatment. In this review, we discuss the ways of FA-albumin conjugation and conjugation of FA to albumin-modified NSPs systems. An application of nanosized and submicron delivery systems on the base of serum albumin and FA for therapy and diagnostics is discussed.