Applications of magnetoliposomes with encapsulated doxorubicin for integrated chemotherapy and hyperthermia of rat C6 glioma.

There is substantial evidence regarding enhanced antitumor cytotoxicity of selected chemotherapeutic agents by appropriate heat exposure (40-44°C). Based upon these results, the integration of hyperthermia as an additional treatment modality given simultaneously with systemic chemotherapy is currently of considerable interest. Hyperthermia can be induced by alternating magnetic field and magnetic nanoparticles. Thus, we have used thermosensitive magnetoliposomes that contained superparamagnetic iron oxide nanoparticles and doxorubicin for in vitro and in vivo therapy of rat glioma C6. The results showed that magnetoliposomes can be specifically heated to 43°C (phase transition temperature of a used lipid composition) in a few minutes, and during this, the encapsulated doxorubicin is released in a controllable manner. The in vitro experiments showed that the cell viability decreased to 79.2% after heat treatment alone and to 47.4% for doxorubicin-loaded magnetoliposomes without application of alternating magnetic field, while the combined treatment resulted in 17.3% cell viability. Also, in vivo results demonstrated that magnetic drug targeting has a strong antiglioma effect with a tumor volume growth inhibition and complete regression. Such targeted delivery and controlled release of anticancer agents would provide clinical advantages compared with currently available methods.

Application of cationized magnetoferritin for magnetic field-assisted delivery of short interfering RNA in vitro.

Cationized magnetoferritin is used for development of a simple, efficient, and fast delivery of short interference RNA into cells using combination of magnetophoresis for pre-concentration of siRNA-magnetoferritin complex on the surface of plated cells with subsequent application of nanosecond laser pulses producing stress waves in transfection chamber, which permeabilize cell membrane for the facilitated delivery of siRNA into the cell interior. As has been quantified using siRNA inducing cell death assay, by combination of these two physical factors we have obtained high efficiency for tested three different human carcinoma cells. Proposed method of gene silencing based on cationized magnetoferritin is a versatile and easily accessible platform with many possible applications in gene therapy.

Application of Albumin-embedded Magnetic Nanoheaters for Release of Etoposide in Integrated Chemotherapy and Hyperthermia of U87-MG Glioma Cells.

BACKGROUND/AIM: Malignant gliomas remain refractory to several therapeutic approaches and the requirement for novel treatment modalities is critical to combat this disease. Etoposide is a topoisomerase-II inhibitor, which promotes DNA damage and apoptosis of cancer cells. In this study, we prepared albumin with embedded magnetic nanoparticles and etoposide for in vitro evaluation of combined hyperthermia and chemotherapy. MATERIAL AND METHODS: Magnetic nanoparticles were prepared by a modified co-precipitation method in the presence of human serum albumin and etoposide. A cellular proliferation assay was used to determine the effects of these nanostructures on the viability of U87 glioma cells in an alternating magnetic field. RESULTS: The in vitro experiments showed that cell viability decreased to 59.4% after heat treatment alone and to 53.8% on that with free etoposide, while combined treatment resulted in 7.8% cell viability. CONCLUSION: Integrating hyperthermia and chemotherapy using albumin co-embedded magnetic nanoheaters and etoposide may represent a promising therapeutic option for glioblastoma.

Influence of naturally occurring antioxidants on magnetic nanoparticles: risks, benefits, and possible therapeutic applications.

We have studied interaction of well known antioxidant L-ascorbic acid with magnetic nanoparticles containing insoluble Fe(III) in their core. In analogy with ferritin, mobilization of iron in the form of water soluble Fe(II) was observed, especially pronounced at higher temperatures. In the presence of hydrogen peroxide cytotoxic hydroxyl radicals are produced. These results suggest possible harmful effects of widely used magnetic nanoparticles as a MRI contrast agents in combination with overload of organism with ascorbic acid in some specific conditions, like fever of patient. On the other hand combination of magnetic nanoparticles and ascorbic acid may be used for a cancer therapy using alternating magnetic field for the release of Fe(II) via Néel relaxation of magnetic moment of used nanoparticles. We have further found that lipoic acid is an efficient antioxidant scavenging hydroxyl radicals produced by Fenton reaction from Fe(II).

Dynamics of magnetic particles in cylindrical Halbach array: implications for magnetic cell separation and drug targeting.

Magnetic nanoparticles for therapy and diagnosis are at the leading edge of the rapidly developing field of bionanotechnology. In this study, we have theoretically studied motion of magnetic nano- as well as micro-particles in the field of cylindrical Halbach array of permanent magnets. Magnetic flux density was modeled as magnetostatic problem by finite element method and particle motion was described using system of ordinary differential equations--Newton law. Computations were done for nanoparticles Nanomag-D with radius 65 nm, which are often used in magnetic drug targeting, as well as microparticles DynaBeads-M280 with radius 1.4 microm, which can be used for magnetic separation. Analyzing snapshots of trajectories of hundred magnetite particles of each size in the water as well as in the air, we have found that optimally designed magnetic circuits of permanent magnets in quadrupolar Halbach array have substantially shorter capture time than simple blocks of permanent magnets commonly used in experiments, therefore, such a Halbach array may be useful as a potential source of magnetic field for magnetic separation and targeting of magnetic nanoparticles as well as microparticles for delivery of drugs, genes, and cells in various biomedical applications.

Magnetic drug delivery and targeting: principles and applications.

BACKGROUND: Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. Magnetic nanoparticles for cancer therapy and diagnosis have been developed on the basis of their unique physico-chemical properties not present in other materials. Their versatility is widely exploited in such diverse techniques as cell and macromolecule separation and purification, immunoassays, targeted drug delivery, controlled material release, electromagnetic hyperthermia, gene therapy, or magnetic resonance imaging. In this review we concentrate on the physical principles of magnetic drug targeting and biomedical applications of this technique. METHODS AND RESULTS: We examined several databases, PubMed, ISI Web of Knowledge, and Scopus, for the period 1985-2009, with specific attention to studies that used targeting of magnetic nanoparticles especially in the therapy and diagnostics of tumors. We have also presented several of our own results on theoretical simulations of magnetic particle motion in external magnetic field. CONCLUSIONS: We found growing number of published papers in this field of nanomedicine, showing the almost unlimited potential of magnetic nanoparticles in the field of experimental and clinical oncology.

Antiulcer activity of water extract of Scoparia dulcis.

Oral treatment with the water extracts of Scoparia dulcis whole aerial parts, at doses of 50, 100 and 200 mg/kg, dose dependently inhibited the indomethacin-induced gastric damages in rats.

Scoparone inhibits ultraviolet radiation-induced lipid peroxidation.

Antioxidant capabilities of scoparone, the component of Artemisia scoparia and other medicinal plants, against lipid peroxidation induced by ultraviolet radiation or Fenton reaction have been analyzed. Lipid peroxidation was monitored by measuring the absorption spectra of the conjugated dienes and quantified by the Klein oxidation index. Obtained results imply that scoparone is a very efficient inhibitor of ultraviolet radiation-induced lipid peroxidation and damage.