Cobalt Ferrite Nanoparticles for Tumor Therapy: Effective Heating versus Possible Toxicity

Magnetic nanoparticles (MNPs) are widely considered for cancer treatment, in particular for magnetic hyperthermia (MHT). Thereby, MNPs are still being optimized for lowest possible toxicity on organisms while the magnetic properties are matched for best heating capabilities. In this study, the biocompatibility of 12 nm cobalt ferrite MNPs, functionalized with citrate ions, in different dosages on mice and rats of both sexes was investigated for 30 days after intraperitoneal injection. The animals’ weight, behavior, and blood cells changes, as well as blood biochemical parameters are correlated to histological examination of organs revealing that cobalt ferrite MNPs do not have toxic effects at concentrations close to those used previously for efficient MHT. Moreover, these MNPs demonstrated high specific loss power (SLP) of about 400 W g−1. Importantly the MNPs retained their magnetic properties inside tumor tissue after intratumoral administration for several MHT cycles within three days. Thus, cobalt ferrite MNPs represent a perspective platform for tumor therapy by MHT due to their ability to provide effective heating without exerting a toxic effect on the organism. This opens up new avenues for smaller MNPs sizes while their heating efficiency is maintained

Centrioles without microtubules: a new morphological type of centriole

The centrosome is the organizing center of microtubules in the cell, the basis for the origin of cilia and flagella and a site for the concentration of a regulatory proteins multitude. The centrosome comprises two centrioles surrounded by pericentriolar material. Centrioles in the cells of different organisms can contain nine triplets, doublets or singlets of microtubules. Here, we show that in somatic cells of male wasp larvae Anisopteromalus calandrae, centrioles do not contain microtubules and are composed of nine electron-dense prongs, which together form a cogwheel structure. These microtubule-free centrioles can be the platform for procentriole formation and form microtubule-free cilia-like structures. In nymph and imago cells centrioles have a microtubule triplet structure. Our study describes how centriole structure differs in a development-stage-dependent and a cell-type-dependent manner. The discovery of a centriole without microtubules casts a new light on the centriole formation process and the evolution of this organelle

Steroid hormones regulate sperm-oviduct interactions in the bovine

After insemination in the cow, a sperm reservoir is formed within the oviducts, allowing the storage then progressive release of spermatozoa toward the ovulated oocyte. In order to investigate the hormonal regulation of these events in vitro, the ovarian steroids 17beta-estradiol (E2) and progesterone (P4) were added at various concentrations to monolayers of bovine oviduct epithelial cells (BOEC) before or during co-incubation with spermatozoa. Main findings demonstrate that: (1) a 18-h pretreatment of BOEC with 100 pg/mL and 100 ng/mL of E2 decreased by 25% the ability of BOEC to bind spermatozoa after 10 min, and for the highest dose of E2, 60 min of co-incubation; (2) P4 at concentrations of 10, 100 and 1000 ng/mL induced the release within 60 min of 32 to 47% of bound spermatozoa from BOEC; this sperm releasing effect was maintained after a 18-h pretreatment of BOEC with 100 pg/mL of E2; (3) E2 in concentrations above 100 pg/mL inhibited the releasing effect of P4 on bound sperm in a dose-dependent manner; (4) spermatozoa bound to then released from BOEC by the action of P4 induced higher cleavage and blastocyst rates after in vitro fertilization than the control group. These results support the hypothesis that the dynamic changes in steroid hormones around the time of ovulation regulate the formation of the sperm reservoir and the timed delivery of capacitated spermatozoa to the site of fertilization

New superparamagnetic fluorescent Fe@C-C5ON2H10-Alexa Fluor 647 nanoparticles for biological applications

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The Centriolar Adjunct–Appearance and Disassembly in Spermiogenesis and the Potential Impact on Fertility

During spermiogenesis, the proximal centriole forms a special microtubular structure: the centriolar adjunct. This structure appears at the spermatid stage, which is characterized by a condensed chromatin nucleus. We showed that the centriolar adjunct disappears completely in mature porcine spermatozoa. In humans, the centriolar adjunct remnants are present in a fraction of mature spermatids. For the first time, the structure of the centriolar adjunct in the cell, and its consequent impact on fertility, were examined. Ultrastructural analysis using transmission electron microscopy was performed on near 2000 spermatozoa per person, in two patients with idiopathic male sterility (IMS) and five healthy fertile donors. We measured the average length of the “proximal centriole + centriolar adjunct„ complex in sections, where it had parallel orientation in the section plane, and found that it was significantly longer in the spermatozoa of IMS patients than in the spermatozoa of healthy donors. This difference was independent of chromatin condensation deficiency, which was also observed in the spermatozoa of IMS patients. We suggest that zygote arrest may be related to an incompletely disassembled centriolar adjunct in a mature spermatozoon. Therefore, centriolar adjunct length can be potentially used as a complementary criterion for the immaturity of spermatozoa in the diagnostics of IMS patients

Investigation of the Antifungal and Anticancer Effects of the Novel Synthesized Thiazolidinedione by Ion-Conductance Microscopy

In connection with the emergence of new pathogenic strains of Candida, the search for more effective antifungal drugs becomes a challenge. Part of the preclinical trials of such drugs can be carried out using the innovative ion-conductance microscopy (ICM) method, whose unique characteristics make it possible to study the biophysical characteristics of biological objects with high accuracy and low invasiveness. We conducted a study of a novel synthesized thiazolidinedione’s antimicrobial (for Candida spp.) and anticancer properties (on samples of the human prostate cell line PC3), and its drug toxicity (on a sample of the human kidney cell line HEK293). We used a scanning ion-conductance microscope (SICM) to obtain the topography and mechanical properties of cells and an amperometric method using Pt-nanoelectrodes to register reactive oxygen species (ROS) expression. All data and results are obtained and presented for the first time

Magnet-Induced Behavior of Iron Carbide (Fe7C3@C) Nanoparticles in the Cytoplasm of Living Cells

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Long-term live cells observation of internalized fluorescent Fe@C nanoparticles in constant magnetic field

International audienceBackground: Theranostics application of superparamagnetic nanoparticles based on magnetite and maghemite isimpeded by their toxicity. The use of additional protective shells significantly reduced the magnetic properties of thenanoparticles. Therefore, iron carbides and pure iron nanoparticles coated with multiple layers of onion-like carbonsheath seem to be optimal for biomedicine. Fluorescent markers associated with magnetic nanoparticles provide reliablemeans for their multimodal visualization. Here, biocompatibility of iron nanoparticles coated with graphite-likeshell and labeled with Alexa 647 fluorescent marker has been investigated.Methods: Iron core nanoparticles with intact carbon shells were purified by magnetoseparation after hydrochloricacid treatment. The structure of the NPs (nanoparticles) was examined with a high resolution electron microscopy.The surface of the NPs was alkylcarboxylated and further aminated for covalent linking with Alexa Fluor 647 fluorochrometo produce modified fluorescent magnetic nanoparticles (MFMNPs). Live fluorescent imaging and correlativelight-electron microscopy were used to study the NPs intracellular distribution and the effects of constant magneticfield on internalized NPs in the cell culture were analyzed. Cell viability was assayed by measuring a proliferative poolwith Click-IT labeling.Results: The microstructure and magnetic properties of superparamagnetic Fe@C core–shell NPs as well as theirendocytosis by living tumor cells, and behavior inside the cells in constant magnetic field (150 mT) were studied.Correlative light-electron microscopy demonstrated that NPs retained their microstructure after internalization bythe living cells. Application of constant magnetic field caused orientation of internalized NPs along power lines thusdemonstrating their magnetocontrollability. Carbon onion-like shells make these NPs biocompatible and enablelong-term observation with confocal microscope. It was found that iron core of NPs shows no toxic effect on the cellphysiology, does not inhibit the cell proliferation and also does not induce apoptosis.Conclusions: Non-toxic, biologically compatible superparamagnetic fluorescent MFMNPs can be further used forbiological application such as delivery of biologically active compounds both inside the cell and inside the wholeorganism, magnetic separation, and magnetic resonance imaging (MRI) diagnostics

Développement de différentes méthodes de microscopie corrélative

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