Iron Oxide Nanoparticles Inhibit Tumor Progression and Suppress Lung Metastases in Mouse Models of Breast Cancer.

Systemic exposure to starch-coated iron oxide nanoparticles (IONPs) can stimulate antitumor T cell responses, even when little IONP is retained within the tumor. Here, we demonstrate in mouse models of metastatic breast cancer that IONPs can alter the host immune landscape, leading to systemic immune-mediated disease suppression. We report that a single intravenous injection of IONPs can inhibit primary tumor growth, suppress metastases, and extend survival. Gene expression analysis revealed the activation of Toll-like receptor (TLR) pathways involving signaling via Toll/Interleukin-1 receptor domain-containing adaptor-inducing IFN-ß (TRIF), a TLR pathway adaptor protein. Requisite participation of TRIF in suppressing tumor progression was demonstrated with histopathologic evidence of upregulated IFN-regulatory factor 3 (IRF3), a downstream protein, and confirmed in a TRIF knockout syngeneic mouse model of metastatic breast cancer. Neither starch-coated polystyrene nanoparticles lacking iron, nor iron-containing dextran-coated parenteral iron replacement agent, induced significant antitumor effects, suggesting a dependence on the type of IONP formulation. Analysis of multiple independent clinical databases supports a hypothesis that upregulation of TLR3 and IRF3 correlates with increased overall survival among breast cancer patients. Taken together, these data support a compelling rationale to re-examine IONP formulations as harboring anticancer immune (nano)adjuvant properties to generate a therapeutic benefit without requiring uptake by cancer cells.

Clinical magnetic hyperthermia requires integrated magnetic particle imaging.

Magnetic nanomaterials that respond to clinical magnetic devices have significant potential as cancer nanotheranostics. The complexities of their physics, however, introduce challenges for these applications. Hyperthermia is a heat-based cancer therapy that improves treatment outcomes and patient survival when controlled energy delivery is combined with accurate thermometry. To date, few technologies have achieved the needed evolution for the demands of the clinic. Magnetic fluid hyperthermia (MFH) offers this potential, but to be successful it requires particle-imaging technology that provides real-time thermometry. Presently, the only technology having the potential to meet these requirements is magnetic particle imaging (MPI), for which a proof-of-principle demonstration with MFH has been achieved. Successful clinical translation and adoption of integrated MPI/MFH technology will depend on successful resolution of the technological challenges discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Physical Activity, Screen Time, and Sleep Duration Among Youth With Chronic Health Conditions in the United States.

PURPOSE: To compare the degree to which youth with and without chronic conditions in the United States met physical activity (PA), screen time, and sleep duration guidelines. DESIGN: A cross-sectional study using data from the 2016 National Survey of Children's Health. PARTICIPANTS: A total of 24 405 youth (aged 10-17 years) with and without 1 of 19 prevalent chronic health conditions who participated in the 2016 National Survey of Children's Health. MEASURES: Parents reported on the time spent by their children in PA, screen time, and sleep. ANALYSIS: Descriptive and bivariate analyses were conducted to estimate and compare health behavior guideline adherence rates among children with and without chronic conditions. RESULTS: Overall, 18.7% of children with chronic conditions did not meet any health behavior guidelines compared to 15.6% of children without chronic conditions. Children with hearing impairments, diabetes, and depression were most likely to not meet any health behavior guidelines (27.9%, 25.4%, and 21.7%, respectively). Of the 3 guidelines, children with and without chronic conditions were least likely to meet the PA guideline (18.6% and 21%, respectively). CONCLUSIONS: This study identifies specific groups of children with chronic conditions that are most at risk of not meeting health behavior guidelines. The findings highlight specific behaviors in most need of intervention for children with chronic conditions; PA was identified as the most frequently unmet guideline. Overall findings suggest a need for a more integrated, holistic view of health promotion for children with chronic conditions.