Molecular Self-assembly Of Cationic/nonionic Surfactants And Their Interaction With DNA

Cationic/nonionic amphiphile mixed systems, have potential in drug delivery and genetherapy. We focus on the self-assembly of cationic/nonionic amphiphile molecules in solutionand the application of amphiphile in the life sciences in the present thesis. We try to elucidatethe molecular mechanism of aggregation and aggregate structures. The main conclusions arelisted as follows:(1) The effects of cationic/nonionic amphiphile total concentration on their interaction withDNA in buffer have been investigated. With increasing the total concentration, the highlystacked dimer structures of DNA are formed, and the base stacking helps to minimize contactof the bases with water, thereby inducing the globule condensation of DNA with smallerZ-average size, and simultaneously the charged phosphate groups of DNA backbone areenclosed in the complexes. Surfactants with a high total concentration are known to promotestronger binding to DNA, which can be related to the balance between hydrophilic andhydrophobic properties.(2) A comparative study on the effects of the cationic/nonionic amphiphile molar ratio on theirinteraction with DNA were conducted by UV spectroscopy, ζ potential and particle sizeinstrument, cryogenic transmission electron Microscopy (Cryo-TEM), atomic forcemicroscopy (AFM), differential scanning calorimetry (DSC), and isothermal titrationmicrocalorimetry (ITC). The results show that the properties of lipoplexes depend on thecharge ratio between the cationic surfactant and DNA, the size and structure of the lipoplexes,and the proportion of nonionic additive (C12E10). Due to the partial protonation and neutralproperties of nonionic surfactant C12E10, either insufficient or excess of C12E10is unfavorableto establish the optimum lipoplexes. The optimum cationic/nonionic surfactant-DNAlipoplexes show a slight positive ζ potential and a mean particle radius small enough to betaken up by the cell at a critical charge ratio (+/). Furthermore, ITC experiments show thatthe entropic contribution to the condensation free energy is maximal and dominant at thispoint. DSC and ITC data show that the aggregation is generally thermodynamically stable,spontaneous, and endothermic, in addition, the equilibrium binding constant (Kb), the binding enthalpy (Hb) and the reaction stoichiometry (n) have been estimated. Cryo-TEM and AFMimages suggest that the lipoplexes initially form “beads-on-a-string” structures, and thenmerge into each other leading to compacted globules upon XC12C6C12Br2gradually increasing.(3) The above studies are base on long-length DNA in the lipoplexes, in this chapter，we focusin the interation between short-length DNA and mixed surfactants. With increasing XC12E10, theabsorption at450nm (A450) of solution initially increased and then decreased. The addition ofC12E10increased surfactants-DNA interaction, and affected the transfection activity dependingon the chain length and the content of PEG in the surfactant. The addition of C12E10providesthe resistance to the size change of the lipoplexes as a stabilizing agent, and resists nearlyneutral complexes aggregating.