Bilayer properties of giant magnetic liposomes formed by cationic pyridine amphiphile and probed by active deformation under magnetic forces

We synthesize giant magnetic liposomes by a reverse-phase evaporation method (REV) using a new self-assembling Cationic Pyridine Amphiphile (CPA) derived from 1,4-dihydropyridine as liposome-forming agent and a magnetic ferrofluid based on $\gamma$ - Fe 2 O 3 nanoparticles. Having in view the potential interest of CPA in targeted transport by magnetic forces, the mechanical elastic properties of such bilayers are here directly investigated in vesicles loaded with magnetic nanoparticles. Bending elastic modulus K b ∼ 0.2 to 5k B T and pre-stress $\tau_{0}$ ∼ 3.2 to 12 . 10-6 erg/cm 2 are deduced from the under-field deformations of the giant magnetic liposomes. The obtained Kb values are discussed in terms of A. Wurgers's theory

Mechanical induction of the tumorigenic b-catenin pathway by tumour growth pressure

International audienceThe tumour microenvironment may contribute to tumorigenesis owing to mechanical forces such as fibrotic stiffness or mechanical pressure caused by the expansion of hyper-proliferative cells 1,2. Here we explore the contribution of the mechanical pressure exerted by tumour growth onto non-tumorous adjacent epithe-lium. In the early stage of mouse colon tumour development in the Notch 1 Apc 1/1638N mouse model, we observed mechanistic pressure stress in the non-tumorous epithelial cells caused by hyper-proliferative adjacent crypts overexpressing active Notch, which is associated with increased Ret and b-catenin signalling. We thus developed a method that allows the delivery of a defined mechanical pressure in vivo, by subcutaneously inserting a magnet close to the mouse colon. The implanted magnet generated a magnetic force on ultra-magnetic liposomes, stabilized in the mesench-ymal cells of the connective tissue surrounding colonic crypts after intravenous injection. The magnetically induced pressure quantitatively mimicked the endogenous early tumour growth stress in the order of 1,200 Pa, without affecting tissue stiffness, as monitored by ultrasound strain imaging and shear wave elastography. The exertion of pressure mimicking that of tumour growth led to rapid Ret activation and downstream phosphorylation of b-catenin on Tyr654, imparing its interaction with the E-cadherin in adhe-rens junctions, and which was followed by b-catenin nuclear trans-location after 15 days. As a consequence, increased expression of b-catenin-target genes was observed at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci. Mechanical activation of the tumorigenic b-catenin pathway suggests unexplored modes of tumour propagation based on mechanical signalling pathways in healthy epithelial cells surrounding the tumour, which may contribute to tumour heterogeneity. To test the tumorous impact of early tumour growth pressure on non-tumorous epithelial tissues in vivo, apart from the mechanical stiffness characteristic of the microenvironment of late tumours 1-

A new bifunctional hybrid nanostructure as an active platform for photothermal therapy and MR imaging

As a bi-functional cancer treatment agent, a new hybrid nanostructure is presented which can be used for photothermal therapy by exposure to one order of magnitude lower laser powers compared to similar nanostructures in addition to substantial enhancment in magnetic resonance imaging (MRI) contrast. This gold-iron oxide hybrid nanostructure (GIHN) is synthesized by a cost-effective and high yield water-based approach. The GIHN is sheilded by PEG. Therefore, it shows high hemo and biocompatibility and more than six month stability. Alongside earlier nanostructures, the heat generation rate of GIHN is compareable with surfactnat-capped gold nanorods (GNRs). Two reasons are behind this enhancement: Firstly the distance between GNRs and SPIONs is adjusted in a way that the surface plasmon resonance of the new nanostructure is similar to bare GNRs and secondly the fraction of GNRs is raised in the hybrid nanostructure. GIHN is then applied as a photothermal agent using laser irradiation with power as low as 0.5 W.cm(−2) and only 32% of human breast adenocarcinoma cells could survive. The GIHN also acts as a dose-dependent transvers relaxation time (T(2)) MRI contrast agent. The results show that the GINH can be considered as a good candidate for multimodal photothermal therapy and MRI