bioreducible liposomes for gene delivery from the formulation to the mechanism of actionbioreducible脂质体基因传递的形成的作用机制.pdf

Bioreducible Liposomes for Gene Delivery: From the Formulation to the Mechanism of Action 1 1 2 1 2 Gabriele Candiani *, Daniele Pezzoli , Laura Ciani , Roberto Chiesa , Sandra Ristori 1 Department of Chemistry, Materials and Chemical Engineering ‘‘Giulio Natta’’, Politecnico di Milano, Milan, Italy, 2 Chemistry Department and Center for Colloid and Surface Science (CSGI), University of Florence, Florence, Italy Abstract Background: A promising strategy to create stimuli-responsive gene delivery systems is to exploit the redox gradient between the oxidizing extracellular milieu and the reducing cytoplasm in order to disassemble DNA/cationic lipid complexes (lipoplexes). On these premises, we previously described the synthesis of SS14 redox-sensitive gemini surfactant for gene delivery. Although others have attributed the beneficial effects of intracellular reducing environment to reduced glutathione (GSH), these observations cannot rule out the possible implication of the redox milieu in its whole on transfection efficiency of bioreducible transfectants leaving the determinants of DNA release largely undefined. Methodology/Principal Findings: With the aim of addressing this issue, SS14 was here formulated into binary and ternary 100 nm-extruded liposomes and the effects of the helper lipid composition and of the SS14/helper lipids molar ratio on chemical-physical and structural parameters defining transfection effectiveness were investigated. Among all formulations tested, DOPC/DOPE/SS14 at 25:50:25 molar ratio was the most effective in transfection studies owing to the presence of dioleoyl chains and phosphatidylethanolamine head groups in co-lipids. The increa