Intracerebral Diffusion of Paramagnetic Cationic Liposomes Containing Gd(DTPA)^2- Followed by MRI Spectroscopy: Assessment of Patternc Diffusion and Time Steadiness of a Non-Viral Vector Model

Abstract

Cationic liposomes are generally considered as the non-viral counterparts of the more common viral vectors used in several gene therapy protocols, but their use as delivery vehicles is limited by their efficiency even if they display a lower toxicity. However, cationic liposomes are promising delivery systems in cell biology due to their ability to incorporate small molecules into their inner aqueous spheres and to deliver them into cells. Additionally, on the external surface they can bind therapeutic molecules such as nucleic acids, oligonucleotides, plasmids, etc. through electrostatic interactions. The aim of this work was to study the diffusion properties of such vehicles in vivo with a non-invasive technique and to monitor their tissue migration in order to collect information to be further used in gene therapy procedures. For this purpose, cationic liposomes containing the paramagnetic contrast agent Gd(DTPA)2- (Gd(III)-diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid) were investigated because of their extended paramagnetic persistency in vivo, compared to the use of the contrast agent alone, and they were used to monitor the diffusion of such vehicles in an animal model (rat model). In particular, these vectors were injected into the rat brain through a stereotactic frame in a preformed cavity mimicking the lesion which had originated after surgical removal of the primary tumor. For the purpose of comparison, the same injection procedure was also applied to a control series of animals without a preformed brain lesion. Pattern diffusion and steadiness of the reported paramagnetic cationic liposomes were studied by means of Magnetic Resonance Imaging (MRI) which allowed us to monitor their diffusion and assess their intracerebral time availability up to 24 hours.

MRI of the basement membrane using charged nanoparticles as contrast agents

“…There is in vitro evidence that CF binds to proteoglycan sites in organs such as heart, eye, and muscle tissue (5, 25, 28, 37–40). Other targets of cationic nanoparticles may exist outside of the kidney, and other cationic probes have been developed to overcome the barriers to delivery (41, 42). Cationization and subsequent uptake at specific sites therefore represents a simple modification of MR contrast agents that may be useful to study specific diseases.…”

The relationship between Bcl-2 gene expression and learning & memory impairment in chronic aluminum-exposed rats

“…Also, Bcl-2 preserves learning and memory by preventing neuronal injury. Takao et al (1995) found that the level of Bcl-2 protein is increased in the hippocampus and cortex of people with dementia of AD (Bei et aL, 2006;Lanzilli et aL, 2006: Masotti et al, 2006. Over-expression of Bcl-2 is associated with preservation of learning and memory, as well.…”

Involvement of NK Cells against Tumors and Parasites

“…It was also shown that NK cells from non-immune individuals can kill plasmodia-infected erythrocytes in the absence of opsonizing antibodies directly through cell-cell interaction, and that this activity was inhibited by anti-FAS antibody and granzyme B inhibitor (55). Furthermore, the finding of children with acute P. falciparum infection suggested a positive correlation between the lytic activity of natural killer cells towards the human leukemia line k562 ex vivo and the extent of parasitemia, and provided evidence that purified NK cells from both healthy and P. falciparum-infected individuals directly lyse parasitized erythrocytes in vitro (56)(57)(58)(59)(60)(61)(62). This optimal activation of NKderived IFN-γ production in vitro requires contact between NK cells and P. falciparum-infected erythrocytes (53).…”