The effect of isovalent substitution of rare-earth cations on the phase separation in half-doped manganites was studied on the example of by high-resolution neutron powder diffraction, neutron beam depolarization, second-harmonic magnetic response, and magnetization and resistivity measurements from 4 K up to room temperature and higher. A structural phase transition from the orthorhombic phase to a mixture of and monoclinic phases was observed upon cooling. The magnetic ground state was found to be phase-separated into three magnetic phases emerging at different temperatures, viz., ferromagnetic (FM) and antiferromagnetic A and charge-ordered CE types. FM clusters arise far above room temperature in the orthorhombic phase and coalesce upon cooling to produce the long-range FM order below 250 K and to arrive at the percolative FM phase below 120 K. The A- and CE-type orders form in the monoclinic phase at the temperatures 200 K and 120 K, respectively. The Sm/Pr isovalent substitution qualitatively changes the phase separation and significantly increases its temperature range compared to the parent compounds. The results obtained give us knowledge of phase separation occurring in systems with strong electron correlations and extend opportunities for fine-tuning of their properties.
Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies because of their tumor-tropism, low immunogenicity, easy accessibility, isolation procedure, and culturing. In the present study, we assessed the tumor-tropism and biodistribution of the superparamagnetic iron oxide nanoparticle (SPION)-labeled MSCs in the orthotopic model of C6 glioblastoma in Wistar rats. As shown in in vitro studies employing confocal microscopy, high-content quantitative image cytometer, and xCelligence system MSCs exhibit a high migratory capacity towards C6 glioblastoma cells. Intravenous administration of SPION-labeled MSCs in vivo resulted in intratumoral accumulation of the tagged cells in the tumor tissues that in turn significantly enhanced the contrast of the tumor when high-field magnetic resonance imaging was performed. Subsequent biodistribution studies employing highly sensitive nonlinear magnetic response measurements (NLR-M2) supported by histological analysis confirm the retention of MSCs in the glioblastoma. In conclusion, MSCs due to their tumor-tropism could be employed as a drug-delivery platform for future theranostic approaches.
Magnetic parameters of magnetosomes inside the bacteria of MSR-1, LBB-42, AMB-1, SP-1, BB-1, and SO-1 strains of the genus Magnetospirillum fixed by 5% formalin in the nutrient medium were estimated by measurements of the nonlinear longitudinal response to a weak ac magnetic field (NLR-M2) at room temperature. For the BB-1, MSR-1, and AMB-1 strains, the measurements of the electron magnetic resonance (EMR) spectra with the special X-band spectrometer for wide-line registration were also carried out. To trace the evolution of the magnetic state of the magnetosomes during the long-term storage, freshly prepared samples (“new”) and samples after a year of storage at 4 °C (“old”) were studied. The assessment of the state of the bacteria ensemble in the medium after the long-term storage was carried out for one typical strain (BB-1) using atomic force microscopy. The stable single-domain state of magnetic centers in the magnetosomes indicating their proximity to a superparamagnetic (SPM) regime was found at the scan frequency 0.02 Hz of the steady magnetic field. This allowed a semi-quantitative analysis of M2 data to be carried out with the formalism based on the numerical solution of the kinetic Fokker–Planck equation for SPM particles. Processing the NLR-M2 data demonstrated the presence of two kinds of magnetosomes in both the “new” and “old” samples: (i) those with the large magnetic moment (the “heavy”, monodisperse mode) and (ii) those with the comparatively small magnetic moment (the “light”, highly dispersed mode). The EMR spectra were formed mostly by the “heavy” fraction for both samples. The presence of two peaks in the spectra evidenced the presence of conventional uniaxial magnetic anisotropy in the magnetosomes. The appearance of one or two additional peaks in the spectra in the “old” fraction of some strains implied their instability at the long-term storage, even when fixed by formalin and sealed in the nitrogen atmosphere.
The development of highly sensitive approaches for detecting tumor cells in biological samples remains a critical challenge in laboratory and clinical oncology. In this study, we investigated the structural and magnetic properties of iron oxide nanoparticles incorporated into cellulose microspheres of two size ranges (~100 and ~700 μm) and evaluated their potential for targeted tumor cell isolation. In the smaller microspheres, magnetite-based magnetic nanoparticles (MNPs) were synthesized in situ via co-precipitation, whereas pre-synthesized MNPs were embedded into the larger microspheres. The geometrical characteristics of the resulting magnetic cellulose microspheres (MSCMNs) were assessed by confocal microscopy. Transmission electron microscopy and X-ray diffraction analyses revealed an average magnetic core size of approximately 17 nm. Magnetic properties of the MNPs within MSCMNs were characterized using a highly sensitive nonlinear magnetic response technique, and their dynamic parameters were derived using a formalism based on the stochastic Hilbert–Landau–Lifshitz equation. To evaluate their applicability in cancer diagnostics and treatment monitoring, the MSCMNs were functionalized with a TKD peptide that selectively binds membrane-associated Hsp70 (mHsp70), yielding TKD@MSCMNs. Magnetic separation enabled the isolation of tumor cells from biological fluids. The specificity of TKD-mediated binding was confirmed using Flamma648-labeled Hsp70 and compared with control alloferone-conjugated microspheres (All@MSCMNs). The ability of TKD@MSCMNs to selectively extract mHsp70-positive tumor cells was validated using C6 glioma cells and mHsp70-negative FetMSCs controls. Following co-incubation, the extraction efficiency for C6 cells was 28 ± 14%, significantly higher than that for FetMSC (7 ± 7%, p < 0.05). These findings highlight the potential of TKD-functionalized magnetic cellulose microspheres as a sensitive platform for tumor cell detection and isolation.