Magnetic Nanoscalpel for the Effective Treatment of Ascites Tumors.

One of the promising novel methods for radical tumor resection at a single-cell level is magneto-mechanical microsurgery (MMM) with magnetic nano- or microdisks modified with cancer-recognizing molecules. A low-frequency alternating magnetic field (AMF) remotely drives and controls the procedure. Here, we present characterization and application of magnetic nanodisks (MNDs) as a surgical instrument ("smart nanoscalpel") at a single-cell level. MNDs with a quasi-dipole three-layer structure (Au/Ni/Au) and DNA aptamer AS42 (AS42-MNDs) on the surface converted magnetic moment into mechanical and destroyed tumor cells. The effectiveness of MMM was analyzed on Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo using sine and square-shaped AMF with frequencies from 1 to 50 Hz with 0.1 to 1 duty-cycle parameters. MMM with the "Nanoscalpel" in a sine-shaped 20 Hz AMF, a rectangular-shaped 10 Hz AMF, and a 0.5 duty cycle was the most effective. A sine-shaped field caused apoptosis, whereas a rectangular-shaped field caused necrosis. Four sessions of MMM with AS42-MNDs significantly reduced the number of cells in the tumor. In contrast, ascites tumors continued to grow in groups of mice and mice treated with MNDs with nonspecific oligonucleotide NO-MND. Thus, applying a "smart nanoscalpel" is practical for the microsurgery of malignant neoplasms.

Magnetic Nanodiscs-A New Promising Tool for Microsurgery of Malignant Neoplasms.

Magnetomechanical therapy is one of the most perspective directions in tumor microsurgery. According to the analysis of recent publications, it can be concluded that a nanoscalpel could become an instrument sufficient for cancer microsurgery. It should possess the following properties: (1) nano- or microsized; (2) affinity and specificity to the targets on tumor cells; (3) remote control. This nano- or microscalpel should include at least two components: (1) a physical nanostructure (particle, disc, plates) with the ability to transform the magnetic moment to mechanical torque; (2) a ligand-a molecule (antibody, aptamer, etc.) allowing the scalpel precisely target tumor cells. Literature analysis revealed that the most suitable nanoscalpel structures are anisotropic, magnetic micro- or nanodiscs with high-saturation magnetization and the absence of remanence, facilitating scalpel remote control via the magnetic field. Additionally, anisotropy enhances the transmigration of the discs to the tumor. To date, four types of magnetic microdiscs have been used for tumor destruction: synthetic antiferromagnetic P-SAF (perpendicular) and SAF (in-plane), vortex Py, and three-layer non-magnetic-ferromagnet-non-magnetic systems with flat quasi-dipole magnetic structures. In the current review, we discuss the biological effects of magnetic discs, the mechanisms of action, and the toxicity in alternating or rotating magnetic fields in vitro and in vivo. Based on the experimental data presented in the literature, we conclude that the targeted and remotely controlled magnetic field nanoscalpel is an effective and safe instrument for cancer therapy or theranostics.

Noninvasive Microsurgery Using Aptamer-Functionalized Magnetic Microdisks for Tumor Cell Eradication.

Magnetomechanical cell disruption using nano- and microsized structures is a promising biomedical technology used for noninvasive elimination of diseased cells. It applies alternating magnetic field (AMF) for ferromagnetic microdisks making them oscillate and causing cell membrane disruption with cell death followed by apoptosis. In this study, we functionalized the magnetic microdisks with cell-binding DNA aptamers and guided the microdisks to recognize cancerous cells in a mouse tumor in vivo. Only 10 min of the treatment with a 100 Hz AMF was enough to eliminate cancer cells from a malignant tumor. Our results demonstrate a good perspective of using aptamer-modified magnetic microdisks for noninvasive microsurgery for tumors.

Some Peculiarities of Humoral Antibacterial Immunity in HIV-infected and AIDS Patients.

The investigation was outlined to study antibodies against some antigens of extracellular microbes associated with inflammation in broncho-pulmonary system and accessory nasal sinus - Staphylococcus aureus, Streptococcus pneumoniae, Branhamella catarrhalis - in individuals (18 patients) with different stages of HIV-infection. The level of antibodies was measured by ELISA and their Ab affinity was assessed by sodium thiocyanate-induced alteration of antibody-antigen interaction. To determine interrelations between antibody production and CD4(+) T lymphocyte number flow cytometry was employed. At the early stages of HIV-infection the levels of antibodies against Streptococcus pneumoniae and GMGM decreased, in comparison with HIV-negative donors. During HIV-infection course levels of antibodies against Staphylococcus aureus peptidoglycan, its antigen determinants and Streptococcus pneumoniae somatic antigen increased. Time affinity of antibodies against these antigens decreased. At all stages of HIV-infection and at all forms of its complications, we observed an increase of titer of antibodies to GMDP, antigenic determinant of peptidoglycan, which carried immunostimulating and adjuvant activities. HIV patients with CD4(+) T lymphocyte number <200 cells/&mgr;l displayed higher level of antibodies to bacterial antigens than that in patients with CD4(+) T lymphocyte number 200-400 per ml. The development of humoral immune response against some of extracellular bacteria is characterized, on the one hand, by their increased levels, and on the other hand, decreased affinity.