Biotargeted nanomedicines for cancer: six tenets before you begin

Biotargeted nanomedicines have captured the attention of academic and industrial scientists who have been motivated by the theoretical possibilities of the ‘magic bullet’ that was first conceptualized by Paul Ehrlich at the beginning of the 20th century. The Biotargeting Working Group, consisting of more than 50 pharmaceutical scientists, engineers, biologists and clinicians, has been formed as part of the National Cancer Institute’s Alliance for Nanotechnology in Cancer to harness collective wisdom in order to tackle conceptual and practical challenges in developing biotargeted nanomedicines for cancer. In modern science and medicine, it is impossible for any individual to be an expert in every aspect of biology, chemistry, materials science, pharmaceutics, toxicology, chemical engineering, imaging, physiology, oncology and regulatory affairs. Drawing on the expertise of leaders from each of these disciplines, this commentary highlights six tenets of biotargeted cancer nanomedicines in order to enable the translation of basic science into clinical practice

Altering Mucus Rheology to “Solidify” Human Mucus at the Nanoscale

The ability of mucus to function as a protective barrier at mucosal surfaces rests on its viscous and elastic properties, which are not well understood at length scales relevant to pathogens and ultrafine environmental particles. Here we report that fresh, undiluted human cervicovaginal mucus (CVM) transitions from an impermeable elastic barrier to non-adhesive objects sized 1 µm and larger to a highly permeable viscoelastic liquid to non-adhesive objects smaller than 500 nm in diameter. Addition of a nonionic detergent, present in vaginal gels, lubricants and condoms, caused CVM to behave as an impermeable elastic barrier to 200 and 500 nm particles, suggesting that the dissociation of hydrophobically-bundled mucin fibers created a finer elastic mucin mesh. Surprisingly, the macroscopic viscoelasticity, which is critical to proper mucus function, was unchanged. These findings provide important insight into the nanoscale structural and barrier properties of mucus, and how the penetration of foreign particles across mucus might be inhibited

Quantitative RT-PCR profiling of the Rabbit Immune Response: Assessment of Acute Shigella flexneri Infection

Quantitative reverse transcription PCR analysis is an important tool to monitor changes in gene expression in animal models. The rabbit is a widely accepted and commonly used animal model in the study of human diseases and infections by viral, fungal, bacterial and protozoan pathogens. Only a limited number of rabbit genes have, however, been analyzed by this method as the rabbit genome sequence remains unfinished. Recently, increasing coverage of the genome has permitted the prediction of a growing number of genes that are relevant in the context of the immune response. We hereby report the design of twenty-four quantitative PCR primer pairs covering common cytokines, chemoattractants, antimicrobials and enzymes for a rapid, sensitive and quantitative analysis of the rabbit immune response. Importantly, all primer pairs were designed to be used under identical experimental conditions, thereby enabling the simultaneous analysis of all genes in a high-throughput format. This tool was used to analyze the rabbit innate immune response to infection with the human gastrointestinal pathogen Shigella flexneri. Beyond the known inflammatory mediators, we identified IL-22, IL-17A and IL-17F as highly upregulated cytokines and as first responders to infection during the innate phase of the host immune response. This set of qPCR primers also provides a convenient tool for monitoring the rabbit immune response during infection with other pathogens and other inflammatory conditions

Patient-reported outcomes for older adults on CamAPS FX closed loop system.

AIMS: Use of the CamAPS FX hybrid closed loop (CL) system is associated with improved time in range and glycated haemoglobin A1c across the age span, but little is known about its effects on patient-reported outcomes (PROs). METHODS: This open-label, randomized, multi-site study compared CamAPS FX to sensor-augmented pump (SAP) in a sample of older adults (≥60 years) with type 1 diabetes (T1D). Thirty-five older adults completed PROs surveys at the start of the study and after each period of 16 weeks using either CL or SAP. At the end of the study, 19 participated in interviews about their experiences with CL. RESULTS: Results examining the 16 weeks of CL use showed that the overall Diabetes Distress Scale score and two subscales (powerlessness and physician distress) improved significantly along with trust on the Glucose Monitoring Satisfaction Survey. User experience interview responses were consistent in noting benefits of 'improved glycaemic control' and 'worrying less about diabetes'. CONCLUSION: In this sample of older adults with T1D who have previously shown glycaemic benefit, there are indicators of improved PROs and subjective user experience benefits.This work was funded by the National Institute of Diabetes and Digestive and Kidney Diseases under the grant number 1DP3DK112176-01. Additional support for the artificial pancreas work from National Institute for Health Research Cambridge Biomedical Research Centre, and JDRF. The University of Cambridge has received salary support for MLE from the National Health Service in the East of England through the Clinical Academic Reserve. Dexcom supplied discounted continuous glucose monitoring devices

Biotargeted nanomedicines for cancer: six tenets before you begin

Biotargeted nanomedicines have captured the attention of academic and industrial scientists who have been motivated by the theoretical possibilities of the ‘magic bullet’ that was first conceptualized by Paul Ehrlich at the beginning of the 20th century. The Biotargeting Working Group, consisting of more than 50 pharmaceutical scientists, engineers, biologists and clinicians, has been formed as part of the National Cancer Institute’s Alliance for Nanotechnology in Cancer to harness collective wisdom in order to tackle conceptual and practical challenges in developing biotargeted nanomedicines for cancer. In modern science and medicine, it is impossible for any individual to be an expert in every aspect of biology, chemistry, materials science, pharmaceutics, toxicology, chemical engineering, imaging, physiology, oncology and regulatory affairs. Drawing on the expertise of leaders from each of these disciplines, this commentary highlights six tenets of biotargeted cancer nanomedicines in order to enable the translation of basic science into clinical practice

Extraordinary Transmission Characteristics of Subwavelength Nanoholes with Rectangular Lattice

We investigate the extraordinary optical transmission (EOT) properties of nanohole arrays with a rectangular lattice for label-free refractive index sensing applications. We show that the deviation within the periodicities along the two axes at the nanohole plane leads to more advantageous spectral quality of EOT signal compared to the conventional square lattice geometries. We introduce a way to further improve the sensitivity of the aperture system by carefully choosing the periodicities. We introduce nanohole arrays with a rectangular lattice supporting EOT signals with larger figure-of-merit values as well as enabling much stronger light transmission. We also model a nanohole system covered with a thin dielectric layer, mimicking biomolecules captured on the gold surface, in order to show its biosensing capability. We also show that certain deviation amounts between periodicities create spectral splitting within the EOT signal leading to larger spectral shifts in the presence of a thin dielectric film. Keywords: Plasmonics, Nanoholes, Extraordinary optical transmission, Rectangular lattice, Label-free biosensin