Polycation liposome-mediated gene transfer in vivo.
ABSTRACT The polycation liposome (PCL), a recently developed gene transfer system, is simply prepared by a modification of liposomes with cetylated polyethylenimine (PEI), and shows remarkable transgene efficiency with low cytotoxicity. In the present study, we investigated the applicability of PCLs for in vivo gene transfer, since the PCL-mediated transgene efficiency was found to be maintained in the presence of serum. PCLs composed of dioleoylphosphatidylethanolamine (DOPE) with 5 mol% cetyl PEI (PEI average mr. wt. 1800), were superior for transfection to those of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (2:1 as molar ratio) with 5 mol% cetyl PEI in vitro, although the latter PCLs were more efficient for gene transfer in vivo. PCL-DNA complexes were injected into mice via a tail or the portal vein, with the DNA being a plasmid encoding green fluorescent protein (GFP) or luciferase; and the expression was monitored qualitatively or quantitatively, respectively. Tail vein injection resulted in high expression of both GFP and luciferase genes in lung, and portal vein injection resulted in high expression of both genes in the liver. Concerning the gene delivery efficiency, the PCL was found to be superior to PEI or cetyl PEI alone. The optimal conditions for in vivo transfection with PCLs were also examined.
[show abstract] [hide abstract]
ABSTRACT: A new method for studying membrane permeance in liposomes is described. The method uses liposomes fabricated to contain IR probe molecules with CN moieties in combination with attenuated total reflection—Fourier transform infrared (ATR-FTIR) spectroscopy. The liposomes are adsorbed on a TiO2 coated ATR crystal and remain intact to flowing aqueous solutions. A change in permeance is determined by monitoring the time dependent decrease in the intensity of a band due to CN groups. It is shown that the transport of the probe molecule depends on the size of the probe molecule and the structure of the liposome membrane. A much clearer molecular understanding of membrane permeance is obtained when the information derived from transport of the probe molecules is combined with the membrane packing arrangement determined from the infrared bands due to the lipids.Biochimica et Biophysica Acta (BBA) - Biomembranes 06/2008; 1778(10):2266-2272. · 3.99 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Do molecularly-targeted contrast agents have what it takes to usher in a paradigm shift as to how we will image cardiovascular disease in the near future? Moreover, are non-invasive vulnerable plaque detection and preemptive treatments with these novel nanoparticulate agents within reach for clinical applications? In this article, we attempt to make a compelling case for how the advent of molecularly-targeted nanoparticle technology may change the way we detect atherosclerotic lesions, determine their clinical significance and even provide non-invasive treatments. Focusing on imaging with cardiovascular MR, an overview of the latest developments in this rapidly evolving field of so-called "intelligent" contrast agents that are able to interrogate the vascular wall and various complementary advanced imaging technologies are presented.Journal of Cardiovascular Magnetic Resonance 02/2007; 9(6):827-43. · 3.72 Impact Factor
Article: A comparison of the behavior of cholesterol, 7-dehydrocholesterol and ergosterol in phospholipid membranes.[show abstract] [hide abstract]
ABSTRACT: A molecular description of the effect of incorporation of cholesterol (CHOL), 7-dehydrocholesterol (7DHC) and ergosterol (ERGO) on the structure of DPPC or EggPC liposomes is provided. Data obtained from ATR-IR spectroscopy, detergent solubility and zeta potential measurements show that the insertion of the various sterols alters the packing arrangement of the tails and headgroup of the PC lipids and may lead to lipid domain formation. On a molecular basis, the differences in lipid packing architecture are traced to differences between the ring and tail structure of the three sterols and these differences in structure produce different effects in DPPC liposomes in the gel phase and EggPC liposomes in the fluid phase. Specifically, CHOL has a relatively flat and linear structure and among the three sterols, shows the strongest molecular interactions with DPPC and EggPC lipids. An extra double bond in the fused ring of 7DHC hinders a tightly packing arrangement with DPPC lipids and leads to less domain formation than CHOL whereas 7DHC clearly produces more lipid domain formation in EggPC. ERGO produces similar structural changes to 7DHC in the tail and headgroup region of DPPC. Nevertheless, ERGO incorporation into DPPC liposomes produces more domain formation than 7DHC.Biochimica et Biophysica Acta (BBA) - Biomembranes 03/2012; 1818(7):1673-1681. · 3.99 Impact Factor