Effective Diagnosis of Foot-And-Mouth Disease Virus (FMDV) Serotypes O and A Based on Optical and Electrochemical Dual-Modal Detection.

Foot-and-mouth disease virus (FMDV) is a highly contagious disease that affects cloven-hoofed animals. The traditional diagnostic methods for FMDV have several drawbacks such as cross-reactivity, low sensitivity, and low selectivity. To overcome these drawbacks, we present an optical and electrochemical dual-modal approach for the specific detection of FMDV serotypes O and A by utilizing a magnetic nanoparticle labeling technique with resorufin ß-d-glucopyranoside (res-ß-glc) and ß-glucosidase (ß-glc), without the use of typical lateral flow assay or polymerase chain reaction. FMDV serotypes O and A were reacted with pan-FMDV antibodies that recognize all seven FMDV serotypes (O, A, C, Asia 1, SAT 1, SAT 2, and SAT 3). The antigen-antibody complex was then immobilized on magnetic nanoparticles and reacted with ß-glc-conjugated FMDV type O or type A antibodies. Subsequently, the addition of res-ß-glc resulted in the release of fluorescent resorufin and glucose owing to catalytic hydrolysis by ß-glc. The detection limit of fluorescent signals using a fluorescence spectrophotometer was estimated to be log(6.7) and log(5.9) copies/mL for FMDV type O and A, respectively, while that of electrochemical signals using a glucometer was estimated to be log(6.9) and log(6.1) copies/mL for FMDV type O and A, respectively. Compared with a commercially available lateral flow assay diagnostic kit for immunochromatographic detection of FMDV type O and A, this dual-modal detection platform offers approximately four-fold greater sensitivity. This highly sensitive and accurate dual-modal detection method can be used for effective disease diagnosis and treatment, and will find application in the early-stage diagnosis of viral diseases and next-generation diagnostic platforms.

Critical Parameters to Improve Pancreatic Cancer Treatment Using Magnetic Hyperthermia: Field Conditions, Immune Response, and Particle Biodistribution.

Magnetic hyperthermia (MH) was used to treat a murine model of pancreatic cancer. This type of cancer is generally characterized by the presence of dense stroma that acts as a barrier for chemotherapeutic treatments. Several alternating magnetic field (AMF) conditions were evaluated using three-dimensional (3D) cell culture models loaded with magnetic nanoparticles (MNPs) to determine which conditions were producing a strong effect on the cell viability. Once the optimal AMF conditions were selected, in vivo experiments were carried out using similar frequency and field amplitude parameters. A marker of the immune response activation, calreticulin (CALR), was evaluated in cells from a xenograft tumor model after the MH treatment. Moreover, the distribution of nanoparticles within the tumor tissue was assessed by histological analysis of tumor sections, observing that the exposure to the alternating magnetic field resulted in the migration of particles toward the inner parts of the tumor. Finally, a relationship between an inadequate body biodistribution of the particles after their intratumoral injection and a significant decrease in the effectiveness of the MH treatment was found. Animals in which most of the particles remained in the tumor area after injection showed higher reductions in the tumor volume growth in comparison with those animals in which part of the particles were found also in the liver and spleen. Therefore, our results point out several factors that should be considered to improve the treatment effectiveness of pancreatic cancer by magnetic hyperthermia.

Personalized dynamic transport of magnetic nanorobots inside the brain vasculature.

Delivering specific bioactive agents with sufficient bioavailability to the targeted brain area across blood brain barrier remains a big challenge. Magnetically driven nanorobots have demonstrated their potential for controlled drug delivery. However, the dynamic transport of these nanorobots inside each individual's brain vasculature is not yet well studied. Addressing this is a critical step forward to controlled drug delivery for non-invasive brain therapeutics. In this paper, we develop an analytical model describing the personalized dynamic transport of spherical magnetic nanorobots inside the brain vasculature reconstructed from the patient's angiography images. By inverting the transporting process, we first design the patient-specific transport path based on the reconstructed vascular model, and then calculate the magnetic force required to drive these nanorobots from the analytical model. Also, a finite element model is created to simulate the inverse design process, which implies that the delivery efficiency of these magnetically driven nanorobots to the targeted brain area can be increased by 20% and almost 95% nanorobots arrive at the desired vessel walls. In the end, a simplified brain vascular model is printed using PolyJet 3D 750 to demonstrate the dynamic transport of these nanorobots toward the targeted site. The proposed theoretical modeling, numerical simulation and experimental validation lay solid foundation toward non-invasive brain therapeutics with maximal accuracy and minimal side effects.

New insights on improved growth and biogas production potential of Chlorella pyrenoidosa through intermittent iron oxide nanoparticle supplementation.

In the present work, the effect of α-Fe2O3-nanoparticles (IONPs) supplementation at varying doses (0, 10, 20 and, 30 mg L-1) at the intermittent stage (after 12th day of growth period) was studied on the growth and biogas production potential of Chlorella pyrenoidosa. Significant enhancements in microalgae growth were observed with all the tested IONPs doses, the highest (2.94 ± 0.01 g L-1) being at 20 mg L-1. Consequently, the composition of the biomass was also improved. Based on the precedent determinations, theoretical chemical oxygen demand (CODth) as well as theoretical and stoichiometric methane potential (TMP, and SMP) were also estimated. The CODth, TMP, SMP values indicated IONPs efficacy for improving biogas productivity. Further, the biochemical methane potential (BMP) test was done for IONPs supplemented biomass. The BMP test revealed up to a 25.14% rise in biogas yield (605 mL g-1 VSfed) with 22.4% enhanced methane content for 30 mg L-1 IONPs supplemented biomass over control. Overall, at 30 mg L-1 IONPs supplementation, the cumulative enhancements in biomass, biogas, and methane content proffered a net rise of 98.63% in biomethane potential (≈ 2.86 × 104 m3 ha-1 year-1) compared to control. These findings reveal the potential of IONPs in improving microalgal biogas production.

Using magnetic particle imaging systems to localize and guide magnetic hyperthermia treatment: tracers, hardware, and future medical applications.

Magnetic fluid hyperthermia (MFH) treatment makes use of a suspension of superparamagnetic iron oxide nanoparticles, administered systemically or locally, in combination with an externally applied alternating magnetic field, to ablate target tissue by generating heat through a process called induction. The heat generated above the mammalian euthermic temperature of 37°C induces apoptotic cell death and/or enhances the susceptibility of the target tissue to other therapies such as radiation and chemotherapy. While most hyperthermia techniques currently in development are targeted towards cancer treatment, hyperthermia is also used to treat restenosis, to remove plaques, to ablate nerves and to alleviate pain by increasing regional blood flow. While RF hyperthermia can be directed invasively towards the site of treatment, non-invasive localization of heat through induction is challenging. In this review, we discuss recent progress in the field of RF magnetic fluid hyperthermia and introduce a new diagnostic imaging modality called magnetic particle imaging that allows for a focused theranostic approach encompassing treatment planning, treatment monitoring and spatially localized inductive heating.

Biodistribution and toxicity of epitope-functionalized dextran iron oxide nanoparticles in a pregnant murine model.

In pursuit of a preventive therapeutic for maternal autoantibody-related (MAR) autism, we assessed the toxicity, biodistribution, and clearance of a MAR specific peptide-functionalized dextran iron oxide nanoparticle system in pregnant murine dams. We previously synthesized ~15 nm citrate-coated dextran iron oxide nanoparticles (DIONPs), surface-modified with polyethylene glycol and MAR peptides to produce systems for nanoparticle-based autoantibody reception and entrapments (SNAREs). First, we investigated their immunogenicity and MAR lactate dehydrogenase B antibody uptake in murine serum in vitro. To assess biodistribution and toxicity, as well as systemic effects, we performed in vivo clinical and post mortem pathological evaluations. We observed minimal production of inflammatory cytokines-interleukin 10 (IL-10) and IL-12 following in vitro exposure of macrophages to SNAREs. We established the maximum tolerated dose of SNAREs to be 150 mg/kg at which deposition of iron was evident in the liver and lungs by histology and magnetic resonance imaging but no concurrent evidence of liver toxicity or lung infarction was detected. Further, SNAREs exhibited slower clearance from the maternal blood in pregnant dams compared to DIONPs based on serum total iron concentration. These findings demonstrated that the SNAREs have a prolonged presence in the blood and are safe for use in pregnant mice as evidenced by no associated organ damage, failure, inflammation, and fetal mortality. Determination of the MTD dose sets the basis for future studies investigating the efficacy of our nanoparticle formulation in a MAR autism mouse model.

Redox-Sensitive Clustered Ultrasmall Iron Oxide Nanoparticles for Switchable T2/T1-Weighted Magnetic Resonance Imaging Applications.

Development of novel activable dual-mode T1/T2-weighted magnetic resonance (MR) contrast agents with the same composition for dynamic precision imaging of tumors has been a challenging task. Here, we demonstrated a strategy to prepare clustered Fe3O4 nanoparticles (NPs) with redox-responsiveness to tumor microenvironment to achieve switchable T2/T1-weighted dual-mode MR imaging applications. In this study, we first synthesized ultrasmall Fe3O4 NPs with an average size of 3.3 nm and an r1 relaxivity of 4.3 mM-1 s-1, and then cross-linked the single Fe3O4 NPs using cystamine dihydrochloride (Cys) to form clustered Fe3O4/Cys NPs. The Fe3O4 nanoclusters (NCs) possess desirable colloidal stability, cytocompatibility, high r2 relaxivity (26.4 mM-1 s-1), and improved cellular uptake efficiency. Importantly, with the redox-responsiveness of the disulfide bond of Cys, the Fe3O4 NCs can be dissociated to form single particles under a reducing condition, hence displaying a switchable T2/T1-weighted MR imaging property that can be utilized for dynamic precision imaging of cancer cells in vitro and a subcutaneous tumor model in vivo due to the reductive intracellular environment of cancer cells and the tumor microenvironment. With the tumor reductive microenvironment-mediated switching of T2 to T1 MR effect and the ultrasmall size of the single particles that can pass through the kidney filter, the developed Fe3O4 NCs may be used as a promising switchable T2/T1 dual-mode MR contrast agent for precision imaging of different biosystems.