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

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

International audienc

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

Développement de différentes méthodes de microscopie corrélative

International audienc

Oviduct extracellular vesicles protein content and their role during oviduct-embryo cross-talk

Successful pregnancy requires an appropriate communication between the mother and the embryo. Recently, exosomes and microvesicles, both membrane-bound extracellular vesicles (EVs) present in the oviduct fluid have been proposed as key modulators of this unique cross-talk. However, little is known about their content and their role during oviduct-embryo dialogue. Given the known differences in secretions by in vivo and in vitro oviduct epithelial cells (OEC), we aimed at deciphering the oviduct EVs protein content from both sources. Moreover, we analyzed their functional effect on embryo development. Our study demonstrated for first time substantial differences between in vivo and in vitro oviduct EVs secretion/content. Mass spectrometry analysis identified 319 proteins in EVs, from which 186 were differentially expressed when in vivo and in vitro EVs were compared (p-value<0.01). Interestingly, 97 were exclusively expressed in in vivo EVs, 47 were present only in in vitro and 175 were common. Functional analysis revealed key proteins involved in sperm-oocyte binding, fertilization and embryo development, some of them lacking in in vitro EVs. Moreover, we showed that in vitro produced embryos were able to internalize in vivo EVs during culture with a functional effect in the embryo development. In vivo EVs increased blastocyst rate, extended embryo survival over time and improved embryo quality. Our study provides the first characterization of oviduct EVs, increasing our understanding of the role of oviduct EVs as modulators of gamete/embryo-oviduct interactions. Moreover, our results point them as promising tools to improve embryo development and survival under in vitro conditions

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

Size-selected Fe3O4–Au hybrid nanoparticles for improved magnetism-based theranostics

Size-selected Fe3O4–Au hybrid nanoparticles with diameters of 6–44 nm (Fe3O4) and 3–11 nm (Au) were prepared by high temperature, wet chemical synthesis. High-quality Fe3O4 nanocrystals with bulk-like magnetic behavior were obtained as confirmed by the presence of the Verwey transition. The 25 nm diameter Fe3O4–Au hybrid nanomaterial sample (in aqueous and agarose phantom systems) showed the best characteristics for application as contrast agents in magnetic resonance imaging and for local heating using magnetic particle hyperthermia. Due to the octahedral shape and the large saturation magnetization of the magnetite particles, we obtained an extraordinarily high r2-relaxivity of 495 mM−1·s−1 along with a specific loss power of 617 W·gFe−1 and 327 W·gFe−1 for hyperthermia in aqueous and agarose systems, respectively. The functional in vitro hyperthermia test for the 4T1 mouse breast cancer cell line demonstrated 80% and 100% cell death for immediate exposure and after precultivation of the cells for 6 h with 25 nm Fe3O4–Au hybrid nanomaterials, respectively. This confirms that the improved magnetic properties of the bifunctional particles present a next step in magnetic-particle-based theranostics