A Validated Methodological Approach to Prove the Safety of Clinical Electromagnetic Induction Systems in Magnetic Hyperthermia.

The present study focuses on the development of a methodology for evaluating the safety of MNH systems, through the numerical prediction of the induced temperature rise in superficial skin layers due to eddy currents heating under an alternating magnetic field (AMF). The methodology is supported and validated through experimental measurements of the AMF's distribution, as well as temperature data from the torsos of six patients who participated in a clinical trial study. The simulations involved a computational model of the actual coil, a computational model of the cooling system used for the cooling of the patients during treatment, and a detailed human anatomical model from the Virtual Population family. The numerical predictions exhibit strong agreement with the experimental measurements, and the deviations are below the estimated combined uncertainties, confirming the accuracy of computational modeling. This study highlights the crucial role of simulations for translational medicine and paves the way for personalized treatment planning.

Self-regulating novel iron oxide nanoparticle-based magnetic hyperthermia in swine: biocompatibility, biodistribution, and safety assessments.

Studies demonstrating the successful and safe application of magnetic hyperthermia in large animals are scarce. A therapeutic approach for advanced cancer comprising multicore encapsulated iron oxide (IO) Sarah Nanoparticles (SaNPs), that uniquely self-regulate their temperature, was developed thus overcoming the safety challenges of hyperthermia. SaNPs are intravenously injected and accumulate in tumor tissue, leading to selective heating upon exposure to an external alternating magnetic field (AMF). A series of studies were conducted in healthy swine to assess SaNPs' safety, alone or combined with AMF application. Administration of single high (up to 22 mg IO/kg) or low (3.6 mg IO/kg) SaNP doses had no adverse effects, including no infusion reactions. Vital signs remained stable with no significant clinical pathology changes, and no treatment-associated toxicities. Biodistribution analysis indicated that SaNPs predominantly accumulate in the lungs and clear in a dose- and time-dependent manner. In minipigs that received a single SaNP no-observed-adverse-effect-level (NOAEL)-based dose (3.6 mg IO/kg) with AMF, the average percentage remaining in vital organs after 90 days was 13.7%. No noticeable clinical signs were noted during the 87 to 92-day observation period following irradiation, and no inflammation, necrosis, nor thermal damage were found in the histopathology evaluation. In another minipig, ~ 90 days after three recurrent high doses (14 mg IO/kg), without AMF, almost half of the injected SaNPs were cleared with no residual detrimental effects. We demonstrate that the approach is safe and well tolerated in swine, opening potential avenues as a novel therapeutic modality for cancer patients.

Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model.

Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect, SaNPs need to accumulate in the tumor. Since the potential accumulation and associated toxicity in normal tissues are an important risk consideration, biodistribution and toxicity were assessed in naïve BALB/c mice. Therapeutic efficacy and the effect on survival were investigated in the 4T1 murine model of metastatic breast cancer. Toxicity evaluation at various timepoints did not reveal any abnormal clinical signs, evidence of alterations in organ function, nor histopathologic adverse target organ toxicity, even after a follow up period of 25 weeks, confirming the safety of SaNP use. The biodistribution evaluation, following SaNP administration, indicated that SaNPs accumulate mainly in the liver and spleen. A comprehensive pharmacokinetics evaluation, demonstrated that the total percentage of SaNPs that accumulated in the blood and vital organs was ~78%, 46%, and 36% after 4, 13, and 25 weeks, respectively, suggesting a time-dependent clearance from the body. Efficacy studies in mice bearing 4T1 metastatic tumors revealed a 49.6% and 70% reduction in the number of lung metastases and their relative size, respectively, in treated vs. control mice, accompanied by a decrease in tumor cell viability in response to treatment. Moreover, SaNP treatment followed by alternating magnetic field exposure significantly improved the survival rate of treated mice compared to the controls. The median survival time was 29 ± 3.8 days in the treated group vs. 21.6 ± 4.9 days in the control, p-value 0.029. These assessments open new avenues for generating SaNPs and alternating magnetic field application as a potential novel therapeutic modality for metastatic cancer patients.

Directed Assembly of Au-Tipped 1D Inorganic Nanostructures via Nanolithographic Docking.

Controlled assembly of nanostructures is a key challenge in nanotechnology. In this work, we introduce an approach for the controlled assembly of 1D nanodumbbells-Au-tipped semiconductor nanorods-into arbitrary 2D higher architectures, by their chemical docking to nanopatterned functionalities. We realized the docking functionalities via nanoimprinted metallic nanodots functionalized with an organic monolayer, whose terminal thiol groups chemically bind the nanodumbbell tips. We demonstrated that the functional nanopattern encodes the nanodumbbell assembly and can be designed to deterministically position nanodumbbells in two possible modes. In the single-docking mode, the nanodot arrays are designed with a spacing that exceeds the nanodumbbell length, restricting each nanodumbbell to dock with one edge and physically connect with its free edge to one of the neighboring nanodumbbells. Alternatively, in the double-docking mode, the nanodots are spaced to exactly fit the nanodumbbell length, allowing nanodumbbell docking with both edges. We found that the docking kinetics can be described by a random attachment model, and verified that for the used docking chemistry, nanodumbbells that are docked to the same dot do not interact with each other. Our work demonstrates the possibility for massively parallel positioning of sub-100 nm 1D semiconductor nanostructures, and can potentially enable their future integration into functional nanodevices and nanosystems.

Organic phase synthesis of noble metal-zinc chalcogenide core-shell nanostructures.

Multi-component nanostructures have been attracting tremendous attention due to their ability to form novel materials with unique chemical, optical and physical properties. Development of hybrid nanostructures that are composed of metal-semiconductor components using a simple approach is of interest. Herein, we report a robust and general organic phase synthesis of metal (Au or Ag)-Zinc chalcogenide (ZnS or ZnSe) core-shell nanostructures. This synthetic protocol also enabled the growth of more compositionally complex nanostructures of Au-ZnSxSe1-x alloys and Au-ZnS-ZnSe core-shell-shell. The optical and structural properties of these hybrid nanostructures are also presented.

Coating and enhanced photocurrent of vertically aligned zinc oxide nanowire arrays with metal sulfide materials.

Hybrid nanostructures combining zinc oxide (ZnO) and a metal sulfide (MS) semiconductor are highly important for energy-related applications. Controlled filling and coating of vertically aligned ZnO nanowire arrays with different MS materials was achieved via the thermal decomposition approach of single-source precursors in the gas phase by using a simple atmospheric-pressure chemical vapor deposition system. Using different precursors allowed us to synthesize multicomponent structures such as nanowires coated with alloy shell or multishell structures. Herein, we present the synthesis and structural characterization of the different structures, as well as an electrochemical characterization and a photovoltaic response of the ZnO-CdS system, in which the resulting photocurrent upon illumination indicates charge separation at the interface.

Studying quantum dot blinking through the addition of an engineered inorganic hole trap.

An all-inorganic compound colloidal quantum dot incorporating a highly emissive CdSe core, which is linked by a CdS tunneling barrier to an engineered charge carrier trap composed of PbS, is designed, and its optical properties are studied in detail at the single-particle level. Study of this structure enables a deeper understanding of the link between photoinduced charging and surface trapping of charge carriers and the phenomenon of quantum dot blinking. In the presence of the hole trap, a "gray" emissive state appears, associated with charging of the core. Rapid switching is observed between the "on" and the "gray" state, although the switching dynamics in and out of the dark "off" state remain unaffected. This result completes the links in the causality chain connecting charge carrier trapping, charging of QDs, and the appearance of a "gray" emission state.