A DNA-transfection protocol has been developed that makes use of thiourea non-cationic synthetic lipid, N-[1,3-bis(carbamothioylamino)propan-2-yl]-2-(dialkycarbamoylmethoxy)acetamide. It was found that these new compounds could be formulated without helper lipid and that the N-decanoyl and N-lauryl derivatives transfected B16 cells in the presence of serum with an efficiency at the same level as cationic lipids, under identical conditions. In vivo transfection using intratumoral injection was also investigated. It was found that compounds 18c and 19 showed an efficiency of the same magnitude as naked DNA and cationic lipid.

Ultracentrifugated compact polyelectrolyte complexes (uCoPECs) represent a new class of materials that are obtained by ultracentrifugation of solutions of polyanion/polycation complexes in the presence of salt. In the present study, two polysaccharides, chitosan and alginate, were used to form such complexes, thus providing a solid material uniquely composed of polysaccharides. The conditions for obtaining the uCoPEC material were optimized: the optimal salt concentration and polysaccharide concentrations were assessed, and the ultracentrifugation speed proved to be a key parameter to obtain compact and homogeneous materials. The Young's modulus, E, of the material was of the order of 12 MPa, which is the highest E value measured for a uCoPEC. The material contained nanometer-sized crystals of chitosan as indicated by X-ray diffraction. Most strikingly, this material proves to be totally cell-and bacteria-resistant. Immunological tests show that this uCoPEC does not induce any proinflammatory response. This makes it a suitable candidate for the development of biocompatible and antifouling biomaterials composed only of polysaccharides.

Cyclic anhydrides are potent tools for bioconjugation, therefore they are broadly used in the functionalization of biomolecules and carriers. The pH-dependent stability and reactivity, as well as the physical properties, can be tuned by the structure of the cyclic anhydride used, thus their application in smart delivery systems has become very important. This review intends to cover the last updates in the use of cyclic anhydrides as pH-sensitive linkers, their differences in reactivity and the latest applications found in bioconjugation chemistry, or chemical biology and when possible, in drug delivery.

No abstract

No abstract

Chemo-mechanotransduction, the way by which mechanical forces are transformed into chemical signals, plays a fundamental role in many biological processes. The first step of mechanotransduction often relies on exposure, under stretching, of cryptic sites buried in adhesion proteins. Likewise, here we report the first example of synthetic surfaces allowing for specific and fully reversible adhesion of proteins or cells promoted by mechanical action. Silicone sheets are first plasma treated and then functionalized by grafting sequentially under stretching poly(ethylene glycol) (PEG) chains and biotin or arginine-glycine-aspartic acid (RGD) peptides. At unstretched position, these ligands are not accessible for their receptors. Under a mechanical deformation, the surface becomes specifically interactive to streptavidin, biotin antibodies, or adherent for cells, the interactions both for proteins and cells being fully reversible by stretching/unstretching, revealing a reversible exposure process of the ligands. By varying the degree of stretching, the amount of interacting proteins can be varied continuously.

DR4 (Death Receptor 4) and DR5 (Death Receptor 5) are two potential targets for cancer therapy due to their ability to trigger apoptosis of cancer cells, but not normal ones, when activated by their cognate ligand TRAIL (TNF related apoptosis-inducing ligand). Therapies based on soluble recombinant TRAIL or agonist antibodies directed against one of the receptors are currently under clinical trials. However, TRAIL-R positive tumor cells are frequently resistant to TRAIL induced apoptosis. The precise mechanisms of this resistance are still not entirely understood. We have previously reported on synthetic peptides that bind to DR5 (TRAILmim/DR5) and induce tumor cell apoptosis in vitro and in vivo. Here, we showed that while hexameric soluble TRAIL is able to efficiently kill the DR5 positive lymphoma Jurkat or the carcinoma HCT116, these cells are resistant to apoptosis induced by the divalent form of TRAILmim/DR5 and are poorly sensitive to apoptosis induced by an anti-DR5 agonist monoclonal antibody. This resistance can be restored by the cross-linking of anti-DR5 agonist antibody but not by the cross-linking of the divalent form of TRAILmim/DR5. Interestingly, the divalent form of TRAILmim/DR5 that induced apoptosis of DR5 positive BJAB cells, acts as an inhibitor of TRAIL-induced apoptosis on Jurkat and HCT116 cells. The rapid internalization of DR5 observed when treated with divalent form of TRAILmim/DR5 could explain the antagonist activity of the ligand on Jurkat and HCT116 cells but also highlights the independence of the mechanisms responsible for internalization and activation when triggering the DR5 apoptotic cascade.

No abstract