Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection and for multi-located tumor sites, i.e. metastases. Non-viral vectors based on the use of cationic lipids or polymers appear to have promising potential, given the problems of safety encountered with viral vectors. Using these non-viral vectors, the current challenge is to obtain a similarly effective transfection to viral ones. Based on the advantages and disadvantages of existing vectors and on the hurdles encountered with these carriers, the aim of this review is to describe the "perfect vector" for systemic gene therapy against cancer.

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Few organisms are able to withstand desiccation stress; however, desiccation tolerance is widespread among plant seeds. Survival without water relies on an array of mechanisms, including the accumulation of stress proteins such as the late embryogenesis abundant (LEA) proteins. These hydrophilic proteins are prominent in plant seeds but also found in desiccation-tolerant organisms. In spite of many theories and observations, LEA protein function remains unclear. Here, we show that LEAM, a mitochondrial LEA protein expressed in seeds, is a natively unfolded protein, which reversibly folds into a-helices upon desiccation. Structural modeling revealed an analogy with class A amphipathic helices of apolipoproteins that coat low-density lipoprotein particles in mammals. LEAM appears spontaneously modified by deamidation and oxidation of several residues that contribute to its structural features. LEAM interacts with membranes in the dry state and protects liposomes subjected to drying. The overall results provide strong evidence that LEAM protects the inner mitochondrial membrane during desiccation. According to sequence analyses of several homologous proteins from various desiccationtolerant organisms, a similar protection mechanism likely acts with other types of cellular membranes.

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This work consisted in defining the in vitro behavior of pegylated lipid nanocapsules (LNC) toward the immune system. LNC were composed of an oily core surrounded by a shell of lecithin and polyethylene glycol (PEG) known to decrease the recognition of nanoparticles by the immune system. The "stealth" properties were evaluated by measuring complement activation (CH50 technique and crossed-immunoelectrophoresis (C3 cleavage)) and macrophage uptake. These experiments were performed on 20-, 50-, and 100-nm LNC before and after dialysis. A high density of PEG at the surface led to very low complement activation by LNC with a slight effect of size. This size effect, associated to a dialysis effect in macrophage uptake, was due to differences in density and flexibility of PEG chains related to LNC curvature radius. Thanks to a high density, 660-Da PEG provided LNC a steric stabilization and a protective effect versus complement protein opsonization, but this protection decreased with the increase of LNC size, especially versus macrophage uptake.