Radioresistant tumours: From identification to targeting.

From surviving fraction to tumour curability, definitions of tumour radioresistance may vary depending on the view angle. Yet, mechanisms of radioresistance have been identified and involve tumour-specific oncogenic signalling pathways, tumour metabolism and proliferation, tumour microenvironment/hypoxia, genomics. Correlations between tumour biology (histology) and imaging allow theragnostic approaches that use non-invasive biological imaging using tracer functionalization of tumour pathway biomarkers, imaging of hypoxia, etc. Modelling dose prescription function based on their tumour radio-resistant factor enhancement ratio, related to metabolism, proliferation, hypoxia is an area of investigation. Yet, the delivery of dose painting by numbers/voxel-based radiotherapy with low lineal energy transfer particles may be limited by the degree of modulation complexity needed to achieve the doses needed to counteract radioresistance. Higher lineal energy transfer particles or combinations of different particles, or combinations with drugs and devices such as done with radioenhancing nanoparticles may be promising.

Characterization of interface properties of fluids by evaporation of a capillary bridge.

The surface properties between two non-miscible fluids are key elements to understand mass transfer, chemistry and bio-chemistry at interfaces. In this paper, surface properties are investigated in evaporating and non-evaporating conditions. A capillary bridge between two large plates (similar to a Hele-Shaw cell) is considered. The temporal evolution of surface forces and mass transfers due to evaporation of the liquid are measured. The force depends on surface properties of the substrate. It is adhesive in the wetting case and repulsive in the non-wetting case. The force is also shown to depend linearly on the volume of the capillary bridge F ∝ V 0 and inversely to the height of the bridge. Modelling is performed to characterize both surface force and evaporation properties of the capillary bridge. The evaporation is shown to be diffusion driven and is decoupled from the bridge mechanics.

Optimization of pegylated iron oxide nanoplatforms for antibody coupling and bio-targeting.

PEGylation has been established as a valuable strategy to minimize nanoparticle clearance by the reticulo-endothelial system due to hydrophilicity and steric repulsion of PEG chains. In this study we functionalized superparamagnetic iron oxide nanoparticle surface with two PEG differing in their length (n = 23 and 44) and terminal functionality, COOH and CH3. By varying the ratio of the two different PEG, we optimized the molecular architecture of the nanoplatform to obtain maximum stability and low toxicity under physiological conditions. The best nanoplatform was evaluated as MRI contrast for mouse brain vascularization imaging at 7 T. The carboxylic acid functions of the nanoplatform were used to covalently bind an antibody, Ab. This antibody, labeled with a fluorophore, targets the ETA receptor, a G-protein-coupled receptor involved in the endothelin axis and overexpressed in various solid tumours, including ovarian, prostate, colon, breast, bladder and lung cancers. In vitro studies, performed by flow cytometry and magnetic quantification, showed the targeting efficiency of the Ab-nanoplatforms. Clearly, an imaging tracer for cancer diagnosis from a bimodal contrast agent (fluorescence and MRI) was thus obtained.

Dextrin-based nanomagnetogel: in vivo biodistribution and stability.

The biodistribution profile of a new dextrin nanomagnetogel, which consists of γ-Fe2O3 superparamagnetic nanoparticles loaded within a polymeric matrix of modified dextrin, was studied in mice. The nanomagnetogel bear a monomodal size distribution profile (average diameter 110 nm) close to neutral surface charge and higher relaxivity (r2 = 215-248 mM(-1) s(-1) and r2/r1 = 13-11) than those of commercial formulations (r2 = 160-177 mM(-1) s(-1) and r2/r1 = 4-7). Also, the observed blood half-life-approximately 4 h-is superior to that of similar commercially available formulations, which remain for a few minutes in circulation. PEGylation resulted in 1.7- and 1.2-fold lower accumulation in the liver and spleen, respectively, within the first 24 h. Noteworthy, a good correlation was obtained between the amount of polymer (quantified by scintigraphy) in the spleen, 48 h after administration, and the amount of iron physically loaded through hydrophobic interactions (quantified by ICP) indicating the absence of iron leakage from the polymeric matrix. This study provides evidence of the in vivo stability of a self-assembled nanomagnetogel, a relevant feature which is seldom reported in the literature.

Endothelin B receptors targeted by iron oxide nanoparticles functionalized with a specific antibody: toward immunoimaging of brain tumors.

In this study, we developed a new bimodal imaging tracer directed against endothelin B receptors to detect brain cancer cells using MRI and to assist tumor surgery with fluorescence imaging. This was achieved by coating the surface of iron oxide nanoparticles with a monoclonal antibody, rendomab-B1, labeled with a fluorescent dye. Two nanoplatforms were elaborated differing by the average number of antibodies grafted onto the nanoparticle surface. The targeting efficiency of these nanoplatforms was validated in vitro. Contrasting MRI properties were highlighted in vivo, demonstrating nanoparticle circulation in the brain through the vasculature.

Synthesis of silver nanoparticles for the dual delivery of doxorubicin and alendronate to cancer cells.

We present the synthesis of a silver nanoparticle (AgNP) based drug-delivery system that achieves the simultaneous intracellular delivery of doxorubicin (Dox) and alendronate (Ald) and improves the anticancer therapeutic indices of both drugs. Water, under microwave irradiation, was used as the sole reducing agent in the size-controlled, bisphosphonate-mediated synthesis of stabilized AgNPs. AgNPs were coated with the bisphosphonate Ald, which templated nanoparticle formation and served as a site for drug attachment. The unreacted primary ammonium group of Ald remained free and was subsequently functionalized with either Rhodamine B (RhB), through amide formation, or Dox, through imine formation. The RhB-conjugated NPs (RhB-Ald@AgNPs) were studied in HeLa cell culture. Experiments involving the selective inhibition of cell membrane receptors were monitored by confocal fluorescence microscopy and established that macropinocytosis and clathrin-mediated endocytosis were the main mechanisms of cellular uptake. The imine linker of the Dox-modified nanoparticles (Dox-Ald@AgNPs) was exploited for acid-mediated intracellular release of Dox. We found that Dox-Ald@AgNPs had significantly greater anti-cancer activity in vitro than either Ald or Dox alone. Ald@AgNPs can accommodate the attachment of other drugs as well as targeting agents and therefore constitute a general platform for drug delivery.

Immobilized Pd on magnetic nanoparticles bearing proline as a highly efficient and retrievable Suzuki-Miyaura catalyst in aqueous media.

A magnetically retrievable nanocatalyst was evaluated for a microwave assisted Suzuki-Miyaura reaction in aqueous media. Excellent yields and conversions were obtained with low Pd loadings (down to 0.01 mol% Pd). It was stable up to 6 months in water under aerobic conditions and efficiency remained unaltered even after 7 repeated cycles.

Outcomes after elective aortic aneurysm repair: a nationwide Danish cohort study 2007-2010.

OBJECTIVE: To assess outcomes after treatment for asymptomatic abdominal aortic aneurysm (AAA) in Denmark in a period when both open surgery (OR) and endoluminal repair (EVAR) have been routine procedures. METHODS: We performed a retrospective nationwide cohort study of patients treated for asymptomatic AAA between 2007 and 2010. Data on demographics, procedural data, perioperative complications, length of stay (LOS), 30-day reinterventions and readmissions, late aneurysm and procedure-related complications and mortality were obtained from the Danish Vascular Registry and the Danish National Patient Register. RESULTS: 525 EVAR and 1176 OR for asymptomatic AAA were identified. LOS was shorter after EVAR than OR (4 vs. 7 days, p < .001). During primary hospitalization procedure-related complications (12% vs. 6%) and general complications (21% vs. 8%) were more common after OR than EVAR (p < 0.001). The 30-day reintervention rate was higher for OR than EVAR (18% vs. 6%, p < 0.001), but there was no difference in readmissions within 30 days. During follow-up (mean 29 ± 15 months) aneurysm-related complications after EVAR were outweighed by procedure-related complications after OR. CONCLUSION: Elective AAA repair in Denmark is overall comparable with international results and both perioperative and late outcomes after EVAR of elective AAA are better than the results after OR.