N. A. Brusentsov

Evaluation of ferromagnetic fluids and suspensions for the site-specific radiofrequency-induced hyperthermia of MX11 sarcoma cells in vitro

Seventeen different ferromagnetic fluids and suspensions were prepared and evaluated for application in radiofrequency-induced hyperthermia. Specific power absorption rates were measured at 0.88 MHz to range from 0 to 240 W per gram of iron for different preparations. Survival of MX11 cells mixed with ferrofluids and subjected to radiofrequency was much lower than with RF without ferrofluid or ferrofluid alone.

Correlation of the coagulation rates and toxicity of biocompatible ferromagnetic microparticles

Interaction of four types of ferromagnetic microparticles with solid phase surfaces in biological media was studied and their acute toxicity compared. Stability of the colloidal system was found to depend on the surface properties, composition and structure of the particles and the solid phase. Increase in stability of the sol leads to decrease in toxicity of the particles.

Ferrimagnetic fluids and ferro- and ferrimagnetic suspensions for the RF-induction hyperthermia of tumors

Ferroand ferrimagnetic induction heating (hyperthermia) of tumors under the action of a radio-frequency (RF) electromagnetic field in the frequency ( f ) range from 0.1 to 1 MHz is used in experimental and clinical hyperthermic oncology [ 1 ]. The RF field comprises a sum of the electric and magnetic field components. The electric component induces electric charges on the surface of materials surrounding experimental animals and the operator [1, 2]. The electric charges may generate electric spark discharges known to be a factor of high toxicity. Protection against the undesired effects of the electric field is provided by the Faraday shield [3]. We have developed a series of ferrimagnetic fluids (FFs), based on dextran ferrite (DF) [ 4 10] and carboxymethyldextran ferrite (CMDF) [9], and ferrimagnetic suspensions (FSs) based on DF, CMDF, and reduced iron powder [ 7 17]. Exposed to an RF electromagnetic field, these media exhibit pyromagnetic properties in accordance with the principle of chemical, structural, and phase complexity [8, 10]. The ferroand ferrimagnetic nuclei in FFs and FSs convert the RF field energy into heat by various energy loss mechanisms, which results in heating of a zone where these nuclei are localized. The rate of heating, or the specific energy absorbed by the nuclei, depends on their size and structure [18]. Coincidence of the FF demagnetization curves measured at 77 and 293 K upon switch-off of the magnetic field indicates that the FF magnetization relaxation is related primarily to rotation of the internal magnetic moments in the particles [19, 20]. The specific absorbed energy and the total

Non‐Invasive in vivo Mapping and Long‐Term Monitoring of Magnetic Nanoparticles in Different Organs of Animals

Quantitative detection of magnetic nanoparticles (MP) in vivo is very important for various biomedical applications. Our original detection method based on non‐linear MP magnetization has been modified for non‐invasive in vivo mapping of the MP distribution among different organs of rats. A novel highly sensitive room‐temperature device equipped with an external probe has been designed and tested for quantification of MP within 20‐mm depth from the animal skin. Results obtained by external in vivo scanning of rats by the probe and ex vivo MP quantification in different organs of rats well correlated. The method allows long‐term in vivo study of MP evolution, clearance and redistribution among different organs of the animal. Experiments showed that dynamics in vivo strongly depend on MP characteristics (size, material, coatings, etc.), site of injection and dose. The developed detection method combined with the magnetic nanolabels can substitute the radioactive labeling in many applications.

Production Technology and Application of Polyfunctional Magnetically Guided Superparamagnetic Preparations (A Review)

Introduction The state-of-the-art in the synthesis of superparamagnetic polyfunctional magnetically guided preparations (PMPs) for the diagnostics and treatment of various disorders is characterized by significant advantages in both experimental and clinical investigations [1 – 126]. Depending on the conditions (in vitro or in vivo, systemic or local), there is a growing need for magnetic preparations, both stable with respect to biogenic factors [20, 21, 35, 40, 64 – 69] and biodegradable [8 – 19, 22 – 34, 38, 42 – 45, 63, 77, 88 – 90], and the corresponding controlled delivery systems [31, 32, 36, 39, 42 – 45]. The major proportion of initial substances [1 – 7, 51, 57] and superparamagnetic PMPs [8 – 115] are obtained by three principal methods [8, 10, 11, 24, 26, 45, 49, 61, 62, 64, 65, 74, 85, 96 – 105] using several variants of the general scheme [113, 115, 117 – 126]: (a) Bis-O-(2,4-trimethylsilyl) derivatives of nucleoside bases + tetra-O-acetyl-D-glucopyranosyl bromide 1-(2,3,4,5-tetra-O-acetyl)-D-glucopyranosides [1 – 7];

DAUNORUBICIN DERIVATIVES OBTAINED FROM DAUNORUBICIN AND NUCLEOSIDE DIALDEHYDES

Abstract Nucleoside dialdehydes were obtained by periodate oxidation of adenosine, cytidine, guanosine, uridine or 6-azauridine in the presence of Dowex (1×8; CH3COO). Reductive alkylation of daunorubicin with these dialdehydes in the presence of NaBH3CN produced a series of 3′-deamino-3′-(4-morpholino)daunorubicin or 13-(R, S)-dihydrodaunorubicin derivatives, the latter being mixtures of two diastereomers at 13-C atom. The morpholino-daunorubicin derivatives containing nucleic base moieties are less cytotoxic than cyanomorpholino-daunorubicin, morpholino-daunorubicin and even than the parent antibiotic.

Physical and chemical criteria for the creation of ferrimagnetic composites for biomedical applications

Previously we reported on the synthesis, analysis, transport, immobilization, antitumor activity, and toxicity of magnetically controlled compounds based on dextran ferrite (DF) composites, comprising microspheroid particles with a diameter of l 0 200 nm, which appear as promising magnetically controlled carriers of antitumor agents [ l -28] . It must be noted that not one of the magnetically controlled antitumor agents obtained so far can satisfy all requirements for preparations intended for intravascular administration [5, 6, 16]. The x-ray diffraction patterns obtained from the initial precipitates of iron oxide, activated ferrite, and DF exhibit intense lines corresponding to the crystal planes (220), (311), (440), and (511) of the cubic structure, with lattice parameters 0.8368, 0.836 l, and 0.8345 nm, respectively [28]. We have obtained DF in the form of microspheroid particles, which differed from their superparamagnetic analogs [7, 8] by ferrimagnetic properties, including high values of the specific saturation magnetization 8 = 2 0 32 A. m2/kg, the residual magnetization fire = 0.5 I. I A 9 m 2 /kg, and the residual coercive force Her = 5 15 mT [24]. The dextran molecules entering into the microspheroid particles of DF form complex compounds with 7-Fe203 microcrystals [ 13 15, 2 2 24]. Because of the existence of chemical bonds between dextran molecules and y-Fe203 microcrystals, the M6ossbauer spectrum of the DF samples differs from those of the initial iron oxide precipitate and activated ferrite by the lack of the central doublet (attributed to the superparamagnetic fraction of Fe 3+ hydroxide) and a strong temperature dependence of the Mt~ossbauer prob-

Magnetic-Fluid Induction Regional Hyperthermia of Sarcoma

Development of magnetic-fluid systems for the hyperthermia of tumors is necessary for increasing the efficiency of multicomponent therapy programs and decreasing the number of inoperable tumors not amenable to treatment because of technical limitations. Recent achievements in the induction hyperthermia therapy of oncologic patients, based on the thermal treatment of tumor tissues at 43 – 45°C, have stimulated further progress in this direction [1]. We have developed a method for the synthesis of magnetic nanoparticles of dextran ferrite (DF) No. 363, which were successfully tested in magnetic-fluid induction regional hyperthermia experiments in vitro [2]. The DF particles in our magnetic fluids, characterized by a low toxicity both in mice (LD50 = 5 g kg at pH 7.4) and in other experimental animals [3], can be considered as the ideal magnetic media for the given purpose [4]. The DF particles dissipate the alternating magnetic field energy via various loss channels and produce hyperthermia in the region of their location [1, 2, 4 – 7]. In the experiments in vitro, the survival of sarcoma MX11 cells as a function of the time of exposure at 44°C for heating provided by magnetic fluids based on DF No. 363 under RF induction treatment at a frequency of 0.88 MHz and a magnetic induction of 7.2 kA m was equivalent to the same exposure on a water bath [2]. A still unsolved technical problem encountered in RF induction hyperthermia in vivo is the difficulty of providing for uniform heating of only the tumor tissue, without any damage to surrounding normal tissues. The purpose of this study was to assess applicability of magnetic fluids (MFs) based on DF No. 363 for RF induction hyperthermia of sarcoma MX11 in vivo at a frequency of 0.88 MHz, a magnetic induction of 9.3 kA m, and a power of 0.15 kW.

Cytotoxicity of Photoheme-Containing Ferrimagnetic Fluid in Alternating Magnetic Field

Ferrimagnetic fluids suitable for magnetothermosensitization (MTS) of tumor cells in ac magnetic field were obtained by mixing photoheme (PH) and dextran ferrite (DF) sols. The mechanisms of the PH + DF-induced MTS most likely involves free-radical processes.

Increase in Photohem Cytotoxicity in a High-Frequency Magnetic Field

The decrease in survivability of cells containing photosensitive substances depends on the degree of excitation [1 – 12]. By the same token, the survival of cells containing magnetically sensitive agents and or substances excited by heating in the dark is determined by the degree of magnetic-field-induced excitation [5, 6] and or the thermal excitation [6, 7]. Hematoporphyrin (HP), its derivatives such as photohem (PH) [1 – 4], and other compounds which, being irradiated by light with a wavelength of 600 – 1000 nm, exhibit electron excitation with the formation of superoxide anions capable of producing singlet oxygen and thus increasing cytotoxicity belong to the class of photosensitizers. Previously, we have developed the PH analog photohem [1 – 4] and used this derivative in the process of photohem-induced magnetothermosensitization (MTS) of cells in the dark. Photohem is capable, by analogy with HP (Fig. 1) [9], of forming superoxide radical anions generating singlet oxygen, an agent destroying tumor cells. In the course of the MTS process, as well as during photosensitization, intercalated photohem particles may increase their ability to generate free radicals. As is known, histidine is capable of trapping singlet oxygen [5, 9]. The increase in the HP-induced damage during tumor cell hyperthermia was inhibited by -carotene (another well-known agent trapping singlet oxygen) or superoxide radical anion (O2 ), but not by mannitol (this agent traps only hydroxyl radicals). Hematoporphyrin and its derivatives also increase the radiosensitizing action of 2-deoxy-D-glucose on tumor cells, probably by reducing the energy spent for the reversible inhibition of DNA repair and increasing cytogenetic damage and tumor cell loss [9 – 11]. An analysis of the literature devoted to photohem (Russia) and its analog photofrin (USA and Canada) showed that