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Accurate and precise delineation of gross tumour volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumours, such as prostate cancer. Magnetic resonance imaging of tumour molecular targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-LINAC. Fibroblast activation protein (FAP) is a transmembrane protein overexpressed in stromal components of >90% of epithelial carcinomas. Herein we compare targeted MRI of gold standard PSMA with FAP in the delineation of orthotopic tumours in a mouse model of prostate cancer. Control (no ligand), FAP and PSMA-targeting iron oxide nanoparticles were prepared with modification of an MRI agent (FerroTrace). Mice with orthotopic LNCaP tumours underwent T2-weighted 3D MRI 24 hours after intravenous injection of contrast agents. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles, which was most pronounced on the tumour periphery. FAP-targeted MRI increased the proportion of tumour contrast enhancing black pixels by 13.37% when compared to PSMA. Furthermore, analysis of changes in R2 values between healthy prostates and LNCaP tumours indicated an increase in contrast enhancing pixels in the tumour border of 15%, when targeting FAP, in contrast to PSMA This study demonstrates preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.

Refereed/Peer-reviewed Understanding the intestinal transport of particles is critical in several fields ranging from optimizing drug delivery systems to capturing health risks from the increased presence of nano- and micro-sized particles in human environment. While Caco-2 cell monolayers grown on permeable supports are the traditional in vitro model used to probe intestinal absorption of dissolved molecules, they fail to recapitulate the transcytotic activity of polarized enterocytes. Here, an intestine-on-chip model is combined with in silico modeling to demonstrate that the rate of particle transcytosis is ≈350× higher across Caco-2 cell monolayers exposed to fluid shear stress compared to Caco-2 cells in standard “static” configuration. This relates to profound phenotypical alterations and highly polarized state of cells grown under mechanical stimulation and it is shown that transcytosis in the microphysiological model is energy-dependent and involves both clathrin and macropinocytosis mediated endocytic pathways. Finally, it is demonstrated that the increased rate of transcytosis through cells exposed to flow is explained by a higher rate of internal particle transport (i.e., vesicular cellular trafficking and basolateral exocytosis), rather than a change in apical uptake (i.e., binding and endocytosis). Taken together, the findings have important implications for addressing research questions concerning intestinal transport of engineered and environmental particles.

Detection of infectious viruses relies on quantitative polymerase chain reaction (qPCR). However, qPCR requires costly equipment, a clean operating environment and experienced technicians, limiting its wide applicability. On the other hand, enzyme-linked immunosorbent assay (ELISA) is widely used in biological laboratories due to its relatively high sensitivity and ease of operation. However, ELISA-based detection of the virus is hampered because it is lower sensitive than qPCR. Herein, a nanoprobe ELISA (NP-ELISA) based on a mesoporous silica nanoprobe, which is constructed by first being loaded with peroxidase and further coated with positively charged polymer polyethyleneimine, and finally functionalized with antivirus antibodies, is designed. Results show that each NP probe is encapsulating 170 peroxidase molecules and presents 200 antibody molecules on the surface. The limit of detection (LOD) of NP-ELISA (LOD = 1450 PFU mL−1) for the detection of real virus samples is tenfold sensitive than that of standard ELISA (LOD = 14, 414 PFU mL−1) and the assay time for NP-ELISA is reduced by 1 h as compared with standard one. Therefore, the NP-ELISA provides a rapid and sensitive immunoassay platform that can readily be implemented for biological laboratory research as well as for on-site clinical diagnostics. Refereed/Peer-reviewed

Microfluidic organs‐on‐chips are rapidly being developed toward eliminating the shortcomings of static in vitro models and better addressing basic and translational research questions. A critical aspect is the dynamic culture environment they provide. However, the associated inherent requirement for controlled fluid shear stress (FSS) and therefore the need for precise pumps limits their implementation. To address this issue, here a novel approach to manufacture pumpless and tubeless organs‐on‐chips is reported. It relies on the use of a hydrophilic thread to provide a driving force for the perfusion of the cell culture medium through constant evaporation in the controlled conditions of a cell incubator. Well‐defined and tuneable flow rates can be applied by adjusting the length and/or diameter of the thread. This approach for the preparation of an intestine‐on‐chip model based on the Caco‐2 cell line is validated. Five days culture under 0.02 dyn·cm−2 shear conditions yield monolayers similar to those prepared using a high‐precision peristaltic pump. A pumpless device can also be used to delineate the effect of FSS on the phenotype of adenocarcinomic human alveolar basal epithelial A549 cells. It is anticipated that the pumpless approach will facilitate and herefore increase the use of organs‐on‐chips models in the future. Refereed/Peer-reviewed

Accurate detection of lymph node metastases is critical for many solid tumours to guide treatment strategies and determine prognostic outcomes. The gold standard for detection of metastasis is by histological analysis of formalin-fixed paraffin-embedded (FFPE) sections of removed lymph nodes; this analysis method has remained largely unchanged for decades. Recent studies have highlighted limitations in the sensitivity of this approach, at least in its current clinical use, to detect very small metastatic deposits. Importantly, the poor prognostic outcomes associated with the presence of such small tumour deposits are now well established in a number of cancers. In addition, histological analysis of FFPE sections cannot be used practically for intraoperative node assessment. Novel lymph node staging technologies are therefore actively being developed. This review critically presents the main advances in this field and discusses why these technologies have not been able to provide a better alternative to the current gold standard diagnostic technique.

Polysaccharides form an important class of natural polymers with critical structural functions and biological activities in plants and all living organisms. It comes as no surprise that polysaccharides are key players in the area of biomaterials, where they have found applications in fi elds as diverse as drug delivery, tissue engineering and regenerative medicine, biosensing and biodiagnostics. Nonetheless, in the early phase of polyelectrolyte multilayers development, up to ~2002, there were only a few studies of layer-by-layer (LbL) assemblies containing polysaccharides. These natural polymers, intrinsically, are more difficult to handle than synthetic polymers or proteins that can be defined precisely in terms of structure, architecture, and molecular weight. Polysaccharides consist of carbohydrate units linked by glycosidic bonds and occur naturally with a range of molecular weights. Specific substituents, such as hydroxyls, sulfates, carboxylates, and amines linked to the glycoside rings, directly control the physicochemical and biological properties of polysaccharides. They also affect the multilayer assembly process, often in unpredictable ways. In addition, polysaccharides undergo facile degradation in strong acidic or alkaline environments. Hence, the multilayer construction conditions need to be selected carefully in order to avoid undesired side-reactions.

Conjugation of PEGylated superparamagnetic nanoparticles with the 3B9 mAb was reported and the specificity of reactions of these novel molecular hybrid medical resonance imaging (MRI) nanoprobes with apoptotic cells was examined. The PEGylated nanoparticles were activated with EDC/NHS and conjugated either with 3B9 or Sal5, an isotype-matched mAb of irrelevant specificity, to achieve immunotargeting. It is found that solvent-free PRGylation process produces nanoparticle aggregates that average 67 mm in diameter with a narrow polydispersity. Antibody immobilization is confirmed by the observation of frequency and dissipation shifts, which are observed after injection of a 100μg/mL 3B9 mAb solution into the flow cell. The concentration of 3B9-nnaoparticles required to reach half saturation is found to be equivalent to 0.65mM of Fe, which corresponds to 7.8nM 3B9 mAb.

Membrane-covered devices could help treat disease of the vasculature such as aneurysm, rupture, and fistulas. They are also investigated to reduce embolic complication associated with revascularization of saphenous vein graft. The aim of this study is to design a clinically applicable biodegradable membrane-covered stent based on the natural polysaccharide chitosan, which has been developed. The mechanical properties of the membrane is optimized through blending with polyethylene oxide (70:30% Wt CH:PEO). The membrane was able to sustain the mechanical deformation of the supporting self-expandable metallic stents during its deployment. The membrane was demonstrated to resist physiological transmural pressure (burst pressure resistance >500 mm Hg) and presented a high-water permeation resistance (1 mL/cm(2) min(-1) at 120 mmHg). The CH-PEO membrane showed a good hemocompatibility in an ex vivo assay. Heparin and hyaluronan surface complexation with the membrane further reduced platelet adhesion by 50.1 and 63% (p = 0.05). The ability of the membrane-covered devices to be used as a drug reservoir was investigated using the nitric oxide donor sodium nitroprusside (SNP). SNP-loaded membranes displayed significantly reduced platelet adhesion.