The comparison between superparamagnetic and ferromagnetic iron oxide nanoparticles for cancer nanotherapy in the magnetic resonance system.

The paper aims to compare zeta potentials, magnetic properties, electron spin resonance, photoluminescence (PL) spectra and antitumor effect of magneto-mechano-chemically synthesized magneto-sensitive nanocomplexes loaded with the anticancer drug doxorubicin (DOXO) during nanotherapy of Walker-256 carcinosarcoma carried out by a magnetic resonance system. Diamagnetic DOXO acquired the properties of a paramagnetic substance after synthesis. MNC comprising superparamagnetic nanoparticles (NP) and DOXO had different g-factors, zeta potentials, a lower saturation magnetic moment, area of the hysteresis loop, and a higher coercivity compared to similar MNC with ferromagnetic NP. The main PL peak of MNC spectrum was defined by DOXO at 598 nm. MNC composed of superparamagnetic NP and DOXO showed a lower standard deviation of the normal PL spectral distribution than MNC based on ferromagnetic NP in relation to conventional DOXO. MNC containing superparamagnetic NP responded to resonance conditions leading to a more pronounced antitumor effect compared to MNC with ferromagnetic NP in the course of magnetic nanotherapy for Walker-256 carcinosarcoma bearing animals (temperature inside the tumor did not exceed 40 °C). Therefore, these findings are associated with differences in chemotherapeutic effect between MNC due to a different surface charge and conformational changes in DOXO molecules during its magnetoelectric interaction with single- and multidomain NP.

Nonlinear Magnetochemical Effects in Nanotherapy of Walker-256 Carcinosarcoma.

The biological and medical aspects of magnetochemical effects in nanotherapy of tumors remain poorly studied. The present paper investigates the influence of nonlinear magnetochemical effects of anisotropic magnetic nanodots on an animal tumor model. The magnetic properties and electron spin resonance spectra of magnetic nanodots and doxorubicin were investigated after mechano-magnetochemical synthesis. The results obtained from the analysis of nonlinear kinetics and survival in Walker-256 carcinosarcoma-bearing animals found a nonlinear dependence between the value of the growth factor, braking ratio, survival rate, tumor redox state, and the treatment by the magnetic nanodot combined with a nonuniform constant magnetic field. To quantify the heterogeneity in microphotographs of Walker-256 carcinosarcoma sections, we applied the entropy parameter. The control (no treatment) group showed the greatest heterogeneity. The lowest value of tumor heterogeneity among animals given treatment was found in groups with the minimum growth factor. Similarly, the lowest entropy value was found in muscle tissue taken from inoculation areas of the tumor. The evidence from this study concluded that inhomogeneous constant magnetic fields with different strength applied to heterogeneous tumor tissues induced different magnetic anisotropy in the magnetic nanodot which had a significant influence on the nonlinear kinetics, redox state, and histological pattern of the tumor.

Nanomagnetic Modulation of Tumor Redox State.

Modulation of reactive oxygen and nitrogen species in a tumor could be exploited for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256 carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe3O4 nanoparticles combined with electromagnetic fields. Treatment using the magnetic nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest antitumor effect with the minimum growth factor 0.49 ± 0.02 day-1 (compared to 0.58 ± 0.02 day-1 for conventional doxorubicin). Electron spin resonance spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an increase of 2.7 times of free iron (that promotes the formation of highly reactive oxygen species), using the nanodot with the largest hysteresis loop area, compared to conventional doxorubicin treatment as well as increases in ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the designed magnetic nanodots can modulate the tumor redox state. We discuss the implications of these results for cancer nanotherapy.

Stomach Cancer: Interconnection between the Redox State, Activity of MMP-2, MMP-9 and Stage of Tumor Growth.

High levels of reactive oxygen (ROS) and nitrogen (RNS) species can lead to the destruction of extracellular matrix facilitating tumor progression. ROS can activate matrix metalloproteinases (MMP), damage DNA and RNA. Therefore, the levels of MMP, ROS and RNS can serve as additional prognostic markers and for the estimation of the effectiveness of tumor therapy. Concerning gastric cancer, the prognostic role of MMP, its connection with the cancer staging remains controversial and correlations between the activity of MMP with the ROS and RNS levels are insufficiently confirmed. Superoxide generation rates, nitric oxide (NO) levels, concentrations of active forms of matrix metalloproteinases MMP-2 and MMP-9 in tumor and adjacent tissues of patients with stomach cancer at different disease stages were measured by electron spin resonance (ESR) including spin-trapping and polyacrylamide gel zymography. It is shown that the activity of MMP-2 and MMP-9 in tumor tissue correlate with the superoxide radicals generation rate and NO levels (r = 0.48÷0.67, p < 0.05). The activity of MMP-2 and MMP-9 in tumor tissues and superoxide radical generation rates correlate positively with the stage of regional dissemination (r = 0.45 and 0.37, correspondingly, p < 0.05), but MMP-2 and MMP-9 activity inversely depends on distant metastatic degree of stomach cancer (r = 0.58; p < 0.05). Additionally, the feasibility of ESR to locally determine oxidative stress is demonstrated.

Magnetic properties and antitumor effect of nanocomplexes of iron oxide and doxorubicin.

We present a technology and magneto-mechanical milling chamber for the magneto-mechano-chemical synthesis (MMCS) of magneto-sensitive complex nanoparticles (MNC) comprising nanoparticles Fe3O4 and anticancer drug doxorubicin (DOXO). Magnetic properties of MNC were studied with vibrating magnetometer and electron paramagnetic resonance. Under the influence of mechano-chemical and MMCS, the complex show a hysteresis curve, which is typical for soft ferromagnetic materials. We also demonstrate that Lewis lung carcinoma had a hysteresis loop typical for a weak soft ferromagnet in contrast to surrounding tissues, which were diamagnetic. Combined action of constant magnetic field and radio frequency moderate inductive hyperthermia (RFH) below 40°C and MNC was found to induce greater antitumor and antimetastatic effects as compared to conventional DOXO. Radiospectroscopy shows minimal activity of FeS-protein electron transport chain of mitochondria, and an increase in the content of non-heme iron complexes with nitric oxide in the tumor tissues under the influence of RFH and MNC.

Acidosis-induced zinc-dependent death of cultured cerebellar granule neurons.

Severe acidosis caused death of cultured cerebellar granule neurons (CGNs). Acidosis was accompanied by a progressive increase of the intracellular zinc ions ([Zn(2+)](i)) and decrease of [Ca(2+)](i). Zn(2+) chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), prevented the increase of [Zn(2+)](i) and acidosis-induced neuronal death. However, neuronal death was insensitive to blockade of ASIC1 channels with amiloride, as CGNs display considerably lower expression of ASIC1a than other neurons. The antioxidant trolox and menadione significantly protected neurons from acidotic death. Earlier, we demonstrated that menadione rescues neurons from the deleterious effect of inhibition of mitochondrial complex I (Isaev et al. Neuroreport 15:2227-2231, 2004). We speculate that excessive Zn(2+)-dependent production of reactive oxygen species by mitochondrial complex I may be a general motive for the induction of cell death in CGNs under acidotic conditions.

Presence of RHD in serologically D-, C/E+ individuals: a European multicenter study.

BACKGROUND: RHD blood group alleles with reduced or absent antigen expression are a clinically significant and heterogeneous group. STUDY DESIGN AND METHODS: To detail population genetics data on apparently D- individuals in central Europe, a six-center study was performed with participants from Austria, Germany, Slovenia, Switzerland, and Russia. A total of 1700 serologically D- samples, positive for C and/or E, were investigated. RESULTS: Observed unexpressed RHD alleles were 59 RHD-CE-D+ hybrid alleles, 9 apparently regular RHD, 1 new RHD(Y401X); DELs were 8 RHD(M295I), 6 RHD(IVS3+1G>A), and 1 new RHD(X418L); and weakly expressed RHDs were 2 weak D type 5, 1 weak D type 1, 1 RHD category VI type 1, and 1 novel weak D type 26. Although weak D type 26 was shown to have one of the lowest D antigen densities ever observed, it gave rise to anti-D immunization in a transfused D- individual. CONCLUSION: The relative occurrence of RHD among serologically D- samples, positive for C and/or E, differed significantly in the investigated central European regions. Considering the growing use of molecular typing techniques, correct identification of blood group alleles with scarce or missing antigen expression is of utmost clinical importance and requires reliable population-based frequency data.

A novel lipopeptide, an inhibitor of bacterial adhesion, from the thermophilic and halotolerant subsurface Bacillus licheniformis strain 603.

A new Bacillus licheniformis strain, 603, isolated from a mixture of drilling fluid and subsurface thermal water, has been found to produce a cyclic lipopeptide which is released into cultural medium as well as present in cells as the major lipid constituent (57% of the total cell lipids extractable with 2:1 chloroform-methanol). The quantitative ratio of the extracellular and intracellular lipopeptide has been estimated as 23:10. The metabolite represents a heptapeptide, L-Asp-->L-Leu-->L-Leu-->L-Val-->L-Val-->L-Glu-->L-Leu, N-acylated to the N-terminal amino acid, L-Asp, by a 3-hydroxy fatty acid (from 13:0 to 17:0 with n-, iso-, and anteiso-chains), the 3-OH group of which is esterified by the C-terminal amino acid, L-Leu. The chemical structure of the lipopeptide has been established by means of infrared (IR), 1H- and 13C-nuclear magnetic resonance (NMR) spectroscopy, electrospray ionisation (ESI) mass spectrometry (MS), including secondary ion mass spectrometry, along with chemical and enzymatic degradation. Although a diversity of similar metabolites synthesised by various B. licheniformis strains are presently known, such a structure has not been reported thus far. Added to the growth medium of strain 603 at the concentration of 1.6 microg/ml, the lipopeptide prevents adhesion of cells to a glass surface. Also, it exhibits a considerable growth-inhibiting activity against Corynebacterium variabilis and a much lower activity against Acinetobacter sp.