- 學位論文
Morphological Diagram of the Electrostatic complexes of DNA with PAMAM G4 Dendrimer
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摘要
Abstract Cationic dendrimers are a potential nonviral vector for gene therapy because of their ability to form electrostatic dendriplexes with DNA as well as their lack of immunogenicity. The structure of the dendriplexes can influence their interactions with cells and hence the transfection efficiency; however, the supramolecular structure of DNA-dendrimer complexes formed under different conditions and its impact on cellular uptake and gene transfection efficiency remain to be explored in detail. Using small angle X-ray scattering, here we show that DNA in the complexes with poly(amidoamine) (PAMAM) G4 dendrimer exhibited four distinct packaging states modulated by the charge density of the dendrimer prescribed by its average degree of protonation (dp, the average number fraction of protonated amine groups in dendrimer). However, we also discuss the effect of charge ratio of the dendriplexes. On this side, we find that decreasing the charge ratio of the dendriplexes affects as increasing the charge density of dendrimer, which means the four distinct packing structures also show up when varying the charge ratio of the dendriplexes. In addition, we also discussed the isotope effect of the dendriplexes. Overall, the various the charge density and charge ratio indeed alter the conformation of the dendriplexes, and we also build a the morphological map of the dendriplexes along two coordinates: charge density of dendrimer” and the “charge ratio” for understanding the effect of these two variations clearly.
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