Nanowarming improves survival of vitrified ovarian tissue and follicular development in a sheep model.

Tissue cryopreservation has allowed long term banking of biomaterials in medicine. Ovarian tissue cryopreservation in particular helps patients by extending their fertility window. However, protection against tissue injury during the thawing process has proven to be challenging. This is mainly due to the heterogenous and slow distribution of the thermal energy across the vitrified tissue during a conventional warming process. Nanowarming is a technique that utilizes hyperthermia of magnetic nanoparticles to accelerate this process. Herein, hyperthermia of synthesized PEGylated silica-coated iron oxide nanoparticles was used to deter the injury of cryopreserved ovarian tissue in a sheep model. When compared to the conventional technique, our findings suggest that follicular development and gene expression in tissues warmed by the proposed technique have been improved. In addition, Nanowarming prevented cellular apoptosis and oxidative stress. We therefore conclude that Nanowarming is a potential complementary candidate to increase efficiency in the ovarian cryopreservation field.

The effect of PEGylated iron oxide nanoparticles on sheep ovarian tissue: An ex-vivo nanosafety study.

Today, nanotechnology plays an important role in our ever-continuous quest to improve the quality of human life. Because of their infinitesimal size, nanostructures can actively interact and alter cellular functions. Therefore, while the clinical benefits of nanotechnology may outweigh most of the associated risks, assessment of the cytotoxicity of nanostructures in respect to cells and tissues early in product development processes is of great significance. To the best of our knowledge, no such assessment has been performed for nanomaterials on the ovarian cortex before. Herein, silica-coated, PEGylated silica-coated, and uncoated iron oxide nanoparticles (IONP) with core diameter of 11 nm (±4.2 nm) were synthesized. The oxidative stress in cultured ovarian tissue exposed to the various IONP was subsequently assessed. The results indicate that among the four groups, uncoated IONP induce the most oxidative stress on the ovarian cortex while tissues treated with PEGylated IONP exhibit no significant change in oxidative stress.

Photothermal enhancement in sensitivity of lateral flow assays for detection of E-coli O157:H7.

Lateral flow immunoassay (LFA) is a well-known point-of-care technology for the detection of various analytes. However, low sensitivity and lack of quantitative results are some of its critical drawbacks. Here we report a photothermal enhanced lateral flow sensor on the basis of the photothermal properties of reduced graphene oxide (rGO) for the detection of E-coli O157:H7 as a model pathogen. The calibration curve of the photothermal method exhibited a linear range from 5 × 105 to 5 × 107 CFU/ml with a correlation coefficient of R2 = 0.96 and a regression equation of y = 8.1x-43 for standard bacteria solutions in phosphate buffer. The limit of detection was ∼5 × 105 CFU/ml for standard bacteria solutions, which was a 10-fold enhancement in sensitivity compared to the qualitative results. Specificity experiments showed that the photothermal method can only detect the target bacteria among 6 types of bacteria strains. It was confirmed that the developed technique could be a highly potential method for the rapid detection field because it can provide fast quantitative results with improved sensitivity.

Co-delivery of miR-181a and melphalan by lipid nanoparticles for treatment of seeded retinoblastoma.

Melphalan is an efficient chemotherapeutic agent that is currently used to treat retinoblastoma (Rb); however, the inherent risk of immunogenicity and the hazardous integration of this drug in healthy cells is inevitable. MicroRNAs are short non-coding single-stranded RNAs that affect a vast range of biological processes. Previously, we focused on the regulatory role of miR-181a during cancer development and progression. In this manuscript, 171 nm switchable lipid nanoparticles (LNP) co-delivered melphalan and miR-181a with encapsulation efficiencies of 93%. Encapsulation of melphalan in LNP significantly improved its therapeutic efficiency. Gene analysis shows that miR-181a decreases the expression of anti-proliferative gene MAPK1 and anti-apoptotic gene Bcl-2, but significantly increased the expression of pro-apoptotic gene BAX. Our results suggest that the two agents have a complementary effect in reducing the viability of cultured Rb cells (primary and cell line) and decreasing Rb cell counts in an in-vivo xenograft Rb model in rats. Our results suggest that the proposed co-delivery technique significantly increases the therapeutic impact, allows for lower administration of melphalan, and consequently, could minimize the cytotoxic side-effects of this drug.

Functionalized reduced graphene oxide as a lateral flow immuneassay label for one-step detection of Escherichia coli O157:H7.

In this study, graphene oxide (GO) and reduced graphene oxide (rGO) were used as visual labels in a lateral flow assay for detection of E. coli O157:H7. The color intensity was employed for the quantitative measurements of the target bacteria. Quantitative results showed that in comparison to GO, rGO can provide higher color intensity owing to enhanced light absorption following chemical reduction. Our results confirm that the visual limit of detection of the target bacteria by rGO is ∼105 colony forming unit per milliliter (CFU/ml), which closely compares with current alternative techniques using gold nanoparticles. The performance and practicability of the rGO-based test strips for detection of the target bacteria in milk and drinking water were validated with conventional plating and colony counting techniques. Results suggest that the proposed lateral flow assay is sensitive, specific, and affordable. It has also the potential to become a widely used detection technique for E. coli O157:H7 and a wide variety of other analytes.

The Dual Regulatory Role of MiR-181a in Breast Cancer.

MicroRNAs (miRNAs) are a family of highly conserved noncoding single-stranded RNA molecules of 21 to 25 nucleotides. miRNAs silence their cognate target genes at the post-transcriptional level and have been shown to have important roles in oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene regulation. Recent evidence indicates that the expression of miR-181a is altered in breast tumor tissue and in the serum of patients with breast cancer. However, there are several contradicting findings that challenge the biological significance of miR-181a in tumor development and metastasis. In fact, some studies have implicated miR-181a in regulating breast cancer gene expression. Here we summarize the current literature demonstrating established links between miR-181a and human breast cancer with a focus on recently identified mechanisms of action. This review also aims to explore the potential of miR-181a as a diagnostic and/or prognostic biomarker for breast cancer and to discuss the contradicting data regarding its targeting therapeutics and the associated challenges.

Hyperthermia of magnetic nanoparticles allows passage of sodium fluorescein and Evans blue dye across the blood-retinal barrier.

PURPOSE: The blood-retina barrier (BRB) is a biological barrier consisting of tightly interconnected endothelial cells inside the retinal vascular network that protects the neural tissue from harmful pathogens and neurotoxic molecules circulating in the bloodstream. Unfortunately, with regard to retinoblastoma, this barrier also prevents systemically administered therapeutics reaching the retinal tissue. In this study we introduce a novel technique to locally and transiently increase BRB permeability for drug delivery using hyperthermia of magnetic nanoparticles (MNPs). MATERIALS AND METHODS: An alternating current (AC) magnetic field was used to induce hyperthermia of locally injected MNPs in the left ophthalmic artery of a rat model. To improve adherence on the surface of the endothelium, commercially available MNPs coated with human transferrin glycoproteins were used. After hyperthermia we assessed the extravasation of systemically injected sodium fluorescein (NaF) as well as Evans blue dye (EBD) into the retinal tissue. RESULTS: Spectrofluorometry and fluorescent microscopy image analysis show a significant increase of dye penetration in the retina where hyperthermia of MNPs was applied. CONCLUSIONS: Our proposed new technique can allow both small and large dye molecules to cross the BRB. While the results are preliminary and thorough evaluation of the retinal tissue following hyperthermia is necessary, this technique has the potential to be an effective mean for the treatment of various diseases such as retinoblastoma.

Remote control of the permeability of the blood-brain barrier by magnetic heating of nanoparticles: A proof of concept for brain drug delivery.

Despite advances in neurology, drug delivery to the brain remains a substantial challenge. This is mainly due to the insurmountable and selective nature of the blood-brain barrier (BBB). In this study, we show that the thermal energy generated by magnetic heating (hyperthermia) of commercially available magnetic nanoparticles (MNPs) in the brain capillaries of rats can transiently increase barrier permeability. Here, the fluorescent Evans Blue (EB) dye was used to verify the BBB integrity. Results indicate a substantial but reversible opening of the BBB where hyperthermia is applied. Also, in this investigation, analysis of CD68 immunoreactivity, an indicator of inflammation, implies that this technique is not associated with any inflammation. We have previously investigated theranostic (therapeutic and diagnostic) capabilities of the MNPs, therefore, the findings presented in this investigation are particularly encouraging for a novel targeted drug delivery system to the brain.

Nitric oxide and cerebrovascular regulation.

The cerebrovascular regulation involves highly complex mechanisms to assure that the brain is perfused at all times. These mechanisms depend on all components of the neurovascular units: neurons, glia, and vascular cells. All these cell types can produce nitric oxide (NO), a powerful vasodilator through different NO synthases. Many studies underlined the key role of NO in the maintenance of resting cerebral blood flow (CBF) as well as in the mechanisms that control cerebrovascular tone: autoregulation and neurovascular coupling. However, although the role of NO in the control of CBF has been largely investigated, the complexity of the NO system and the lack of specific NO synthase inhibitors led to still unresolved questions such as the origin of NO and the pathways by which it controls the vascular tone. In this chapter, the role of NO in the regulation of CBF is critically reviewed and discussed in the context of the neurovascular unit and the general principles of cerebrovascular regulation.

Towards MR-navigable Nanorobotic Carriers for Drug Delivery into the Brain.

Magnetic Resonance Navigation (MRN) relies on Magnetic Nanoparticles (MNPs) embedded in microcarriers or microrobots to allow the induction of a directional propelling force by 3-D magnetic gradients. These magnetic gradients are superposed on a sufficiently high homogeneous magnetic field (e.g. the Bo field of a MR scanner) to achieve maximum propelling force through magnetization saturation of the MNPs. As previously demonstrated by our group, such technique was successful at maintaining microcarriers along a planned trajectory in the blood vessels based on tracking information gathered using Magnetic Resonance Imaging (MRI) sequences from artifacts caused by the same MNPs. Besides propulsion and tracking, the same MNPs can be synthesized with characteristics that can allow for the diffusion of therapeutic cargo carried by these MR-navigable carriers through the Blood Brain Barrier (BBB) using localized hyperthermia without compromising the MRN capabilities. In the present study, localized hyperthermia induced by an alternating magnetic field (AC field) is investigated for the purpose of transient controlled disruption of the BBB and hence local delivery of therapeutic agents into the brain. Here, an external heating apparatus was used to impose a regional heat shock on the skull of a living mouse model. The effect of heat on the permeability of the BBB was assessed using histological observation and tissue staining by Evans blue dye. Results show direct correlation between hyperthermia and BBB leakage as well as its recovery from thermal damage. Therefore, in addition to on-command propulsion and remote tracking, the proposed navigable agents could be suitable for controlled opening of the BBB by hyperthermia and selective brain drug delivery.