In this paper, we developed a promising technique for luminescent infrared (IR) diagnostics of neoplasms of visually and endoscopically accessible localization (dermatology, gynecology, dentistry) using ytterbium complexes of porphyrins. Possible mechanisms of accumulation of a pharmaceutical composition based on the ytterbium complex of 2,4-di(α-methoxyethyl)deuteroporphyrin IX (Yb-DMDP) in tumor tissues were studied. Studies on the pharmacokinetics and biodistribution of this substance in various organs and neoplasms of laboratory animals showed a significant selectivity of the accumulation of nanoparticles with ytterbium ions in tumors as early as 24 h after intravenous administration. For the purposes of luminescent IR diagnostics, a highly sensitive laser-fiber fluorimeter operating in the spectral range of 900–1100 nm was developed. Preclinical tests of the developed method of fluorescent IR cancer diagnostics were carried out and its prospects were shown.

In this paper, we developed a promising technique for luminescent infrared (IR) diagnostics of neoplasms of visually and endoscopically accessible localization (dermatology, gynecology, dentistry) using ytterbium complexes of porphyrins. Possible mechanisms of accumulation of a pharmaceutical composition based on the ytterbium complex of 2,4-di(α-methoxyethyl)deuteroporphyrin IX (Yb-DMDP) in tumor tissues were studied. Studies on the pharmacokinetics and biodistribution of this substance in various organs and neoplasms of laboratory animals showed a significant selectivity of the accumulation of nanoparticles with ytterbium ions in tumors as early as 24 h after intravenous administration. For the purposes of luminescent IR diagnostics, a highly sensitive laser-fiber fluorimeter operating in the spectral range of 900–1100 nm was developed. Preclinical tests of the developed method of fluorescent IR cancer diagnostics were carried out and its prospects were shown.

In this paper we develop the fundamentals of a promising method of magnetoluminescent theranostics of tumors with visually and endoscopically accessible localization. The method is based on the use of composite nanoparticles consisting of a Lexan-type polymer matrix (nanocomposite shell) with incorporated ytterbium complexes of porphyrins (a hydrophobic ytterbium complex of hematoporphyrin IX tetramethyl ether), as well as magnetite nanoparticles. In this case, nanoparticles of the ytterbium porphyrin complex incorporated into the polymer matrix are responsible for carrying out the process of luminescent tumor diagnostics while magnetite nanoparticles provide tumor therapy through magnetic hyperthermia. The optimal size range of magnetic nanoparticles used in this method is shown to be d = 10–20 nm. Studies on the biodistribution of the nanocomposite in various organs and tumors of laboratory animals (female mice of the Bulb/c line with transplanted Ehrlich carcinoma) showed a significant selectivity of the accumulation of nanoparticles in the tumor as early as 24 h after intravenous administration.

This paper describes the synthesis method and the spectral-luminescent properties of nanoparticles containing the ytterbium complex of protoporphyrin IX dimethyl ether in Lexan-based polymer matrix which are promising for use in tumours diagnostics. For theranostics purposes, the synthesis of multifunctional nanoparticles containing iron oxide core and Lexan-polymer shell, including ytterbium porphyrin complexes (YPC), was carried out. The iron oxide nanoparticles are responsible for carrying out the local hyperthermia procedure when exposed to a high-frequency magnetic field.

Acoustic plasma discharge and cavitation in aqueous solutions were used to prepare metal oxide nanoparticles (NPs) based on tungsten, copper, iron and zinc. It was found that ultrasonic cavitation during the NP formation influenced strongly the size and physical properties of NPs, which were measured by means of the electron microscopy, dynamic light scattering (DLS) and photoluminescence (PL) techniques. In vitro studies did not reveal cytotoxicity of the NPs for concentration of up to 0.2 mg/mL and exposure time for one week. The obtained results indicate good prospects of the prepared NPs for biomedical applications in the PL diagnostics of cancer and magnetic hyperthermia.

The water-based magnetite Fe3O4, maghemite gamma-Fe2O3, Gd-substituted ferrites Fe[GdxFe2 (x)] O-4, Ni-Cu alloy particles suspensions and dextran-ferrite (DF) solutions were prepared for the magnetically controlled thermochemotherapy (MCT). The temperature elevation prepared nanoparticles in AC magnetic field (0.88 MHz, 7.3 kA/m, 0.15 kW) and their toxicity were characterised. The results are in a good agreement with physical and chemical properties observed by in vitro measurements. The moment and Curie temperature of magnetic nanoparticles are obtained. The corresponding models of magnetic structure for magnetite, maghemite and Gd-doped ferrites are discussed.

We review our recently obtained data on the employment of Si nanoparticles as sensitizers of radiofrequency (RF) induced hyperthermia for mild cancer therapy tasks. Such an approach makes possible the heating of aqueous suspensions of Si nanoparticles by tens of degrees Celsius under relatively low intensities (1-5 W/cm2) of 27 MHz RF radiation. The heating effect is demonstrated for nanoparticles synthesized by laser ablation in water and mechanical grinding of porous silicon, while laser-ablated nanoparticles demonstrate a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations. The observed RF heating effect can be explained in the frame of a model considering the polarization of Si NPs and electrolyte in the external oscillating electromagnetic field and the corresponding release of heat by electric currents around the nanoparticles. Our tests evidence relative safety of Si nanostructures and their efficient dissolution in physiological solutions, suggesting potential clearance of nanoparticles from a living organism without any side effects. Profiting from Si nanoparticle-based heating, we finally demonstrate an efficient treatment of Lewis Lung carcinoma in vivo. The obtained data promise a breakthrough in the development of mild, non-invasive methods for cancer therapy.

The experiments on the impact of the size of magnetite clusters on various magnetic properties (magnetic moment, Curie temperature, blocking temperature etc.) have been carried out.The methods of magnetic separation, centrifuging of water suspensions of biocompatible iron oxide nanoparticles (NPs) allow producing fractions with diameter of nanoparticles in the range of 4÷22 nm.The size of NPs are controlled by the methods of dynamic light scattering (DLS), transmission electron microscopy (TEM) and atomic force microscopy (AFM).For the first time the DLS method is applied in real time to control the size during the process of the separation of the NPs in aqueous suspensions.The changes of the size of NPs cause a shift in the Curie temperature and in the changes in the specific magnetic properties of the iron NPs.The experimental data is interpreted on the basis of Monte Carlo simulations for the classical Heisenberg model with different bulk and surface magnetic moments.It is demonstrated experimentally and by theoretical modeling that magnetic properties of magnetite NPs are determined not only by their sizes, but also by the their surface spin states, while both growing and falling dependences of the magnetic moment (per Fe 3 O 4 formula unit) being possible, depending on the number of magnetic atoms in the nanoparticle.Both NPs clean and covered with a bioresorbable layer clusters have been investigated.

In the course of the recent development of new sol-gel derived materials for optics, organically modified metal oxide matrices have widely demonstrated their great potential. Most of the work performed in this area has been concentrated on embedding organic or organo-metallic chromophores in an oxide network to make optical devices. The main advantages of the use of hybrid organic—inorganic nanocomposites result from their high versatility in offering a wide range of possibilities to fabricate tailor-made materials in terms of their chemical and physical properties, and macroscopic shape molding. Such materials emerging in this field are known as ‘sol-gel photonics’. There have been some striking examples of the use of room temperature processed hybrids to design materials with emission, absorption, second-order nonlinear optical and photochromic properties.

Two electrophoretically distinguishable isoforms of Dj-1 protein have been identified in a proteomic study of tissue specimens obtained from patients with confirmed prostate cancer (PCa) and benign prostatic hyperplasia (BPH). Dj-1 was also found in the cell lines PC-3, DU-145, LNCaP, BPH-1, and the lowest level of Dj-1 was found in BPH-1. An immunochemical study (ELISA) of serum levels of Dj-1, Bcl-2, IGF-1 and IGFBP-3 proteins revealed statistically significant differences between these two groups of patients only for Dj-1 (p = 0.004, the Wilcoxon-Mann-Whitney test). These data suggest that Dj-1 protein is a perspective candidate biomarker for PCa.

Composite nanoparticles consisting of gold-silver nanocages coated by mesoporous silicon dioxide and functionalized with a photodynamic sensitizer of the Yb-2,4-dimethoxyhematoporphyrin IX dipotassium salt (Yb-HP; about 70000 molecules per one particle) are obtained for the first time. The synthesis technology makes it possible to control the nanocage size in a range of 40–60 nm and the silica shell thickness from 20 to 100 nm. In addition to the known plasmon resonance near 750–800 nm, the composite nanoparticles exhibit an additional absorbance peak at about 400 nm, corresponding to free Yb-HP, and characteristic visible fluorescence bands near 580 and 630 nm, which correspond to the optical features of the bound Yb-HP. The presence of an additional IR luminescence band of the Yb3+ ion in the range of 900–1100 nm is used to control the accumulation and biodistribution of composite conjugates with the help of the IR luminescence method in the spectral window of the tissue. Comparative data on the biodistribution of free Yb-HP and Yb-HP luminescent conjugates are presented after intravenous injection in mice with grafted Ehrlich carcinoma tumors. The accumulation contrast in the tumors 24 h after injection is shown using the IR luminescence technique.

The equilibrium dissociation constants KD, the complex association / dissociation rate constants (k on /k off) and lifetimes of the complexes of redox partners were measured for three cytochrome P450-containing monooxygenase systems (P450cam, P450scc, and P450 2B4) under hydroxylation conditions. The Q parameter representing the ratio of protein-protein complex lifetime (τ lT ) to time required for a single hydroxylation cycle (τturnover) was introduced for estimation of productivity of complexes formed within the systems studied. The Q parameter was insignificantly changed upon transition from the oxidation to hydroxylation conditions. Lifetimes (τ lT ) for the binary complexes formed within the P450cam and the P450scc systems obligatory requiring an intermediate electron transfer protein between the reductase and cytochrome P450 could not realize hydroxylation reactions for substrates with known τturnover and so they were non-productive while the binary complexes formed within the P450 2B4 system, not requiring such intermediate electron-transfer protein, appeared to be productive. Formation of ternary complexes was demonstrated under hydroxylation conditions in all three systems. Analysis of Q values led to the conclusion that the ternary complexes formed within the P450cam and the P450scc systems were productive. In the case of the P450 2B4 system, more than half (about 60%) ternary complexes were also found to be productive.

The interaction sites for protein partners, cytochrome P450 2B4 (d-2B4) and NADPH: cytochrome P450 reductase (d-Fp), have been identified. These proteins form complexes during their functioning. Nonspecific covalent cross-linking of the d-2B4 complexes with d-Fp in the Emulgen 913 monomerized system was achieved by 4,4′- dithiobis-phenyl azide. Covalently cross-linked peptides of this complex were identified by ESI-MS/MS. Several binding sites have been identified for these proteins. Based on these sites a model for intermolecular interaction between these proteins has been proposed. This model includes 5 contact sites on d-2B4 for d-Fp (stabilized by the cross-linker); these include the following pairs of corresponding peptides of d-2B4 and d-Fp: 1) d-2B4324–336 and d-Fp570–585; 2) d-2B4423–433 and d-Fp102–109; 3) d-2B4327–336 and d Fp452–464; 4) d-2B4192–197 and d-Fp456–464; 5) d-2B4134–139 and d-Fp406–425. In the two last cases d-Fp peptides are located in the interdomain cleft and stabilize the protein-protein complex via the cross-linker and so the d 2B4/d-Fp complex formation by these sites may involve amino acid residues of the peptides d-Fp456–464 and d-Fp406–425, which surround the interdomain cleft.

The interactions between cytochrome P450 2B4 (d-2B4), NADPH:cytochrome P450 reductase and cytochrome b5 have been investigated in the monomeric reconstituted P450 2B4-containing monooxygenase system in the presence of a substrate (7-pentoxyresorufin) and an electron donor, NADPH. Each partner was immobilized via its amino groups on the carboxymethyldextran biochip surface of the optical biosensor IAsys+. Such mode immobilization was not accompanied by any loss of activities of the immobilized proteins. The formation of binary d-Fp/d-2B4 complexes was registered. The association/dissociation rate constants (kon/koff) were (0.013 ± 0.005) × 106 M−1 s−1/0.05 ± 0.02 s−1, and dissociation constant (KD) was (0.26 ± 0.13) × 10−6 M. Comparison of kon, koff and KD values for d-Fp/d-2B4 complexes formed under hydroxylation (O-dealkylation) with corresponding constants obtained for the oxidized proteins of (0.10 ± 0.03) × 106 M−1 s−1/(0.14 ± 0.06) s−1, and (0.71 ± 0.37) × 10−6 M, respectively shows that the decrease in kon and an insignificant decrease in KD are associated with the increase of complex lifetime during transition from the oxidized to hydroxylation conditions. Complex formation between d-Fp and d-b5 was not registered in both hydroxylation conditions and in the case of oxidized forms of these proteins. In both cases formation of the ternary d-Fp/d-2B4/d-b5 complexes occurred.

Early detection of premalignant/malignant lesions in the oral cavity can certainly improve the patient’s prognosis. This study presents fluorescence imaging with the topical application of 5-aminolevulinic as a way to improve detection of various oral tissue pathologies. This procedure depends mainly on comparing the intensity of red and green fluorescence emitted from tissues during examination.Seventy-one patients who presented with clinically suspicious oral leukoplakia were recruited for this study. Each of the patients was required to have 5-aminolevulinic acid in the form of mouth rinse prior to fluorescence imaging. Following this a surgical biopsy was acquired from the exact examination site. The results of the fluorescence spectroscopy have been compared with histopathology.A Student’s t-test was applied to test the viability of the ratio between red and green fluorescence. The red-to-green ratio was found to increase significantly when the lesion was identified as dysplastic or carcinoma in situ. By applying a threshold line to discriminate between normal and dysplastic lesions; a sensitivity of 83–90% and specificity of 79–89% were obtained.Fluorescence spectroscopy combined with 5-aminolevulinic acid-induced protoporphyrin IX was found as a valuable tool in the diagnosis of oral premalignancy. This technique offers the potential to be advantageous over other non-optical techniques in terms of providing real-time diagnosis, in situ monitoring, cost effectiveness and more tolerated by patient compared to surgical biopsy.

The multiparametric physical method for diagnosis and test of curing cancer diseases based on Rayleigh light scattering is proposed. There was studied simultaneously dynamic and static parameters of blood plasma and serum proteins. A special device for this purpose is described and clinical results are presented.