ABSTRACT
Polyamidoamine (PAMAM) dendrimers (Figure 76) are a class of synthetic, highly branched, spherical molecules with dened chemical functionality (Tomalia, 1993; Cagin et al., 2000; Li et al., 2000). These molecules are uniform in size and constructed from various initiator cores on which each complete iterative reaction sequence results in a new dendrimer generation. The molecular weight of the dendrimer hence increases exponentially, the number of primary amine surface groups exactly doubles, and the diameter increases by ~10 Å. These generations are covalently attached, thus yielding a 3D highly ordered polymeric compounds (Ottaviani et al., 1998) of 10-130 Å in diameter for generation 0 through generation 10. Generally, PAMAM dendrimers have been determined to be nonimmunogenic and exhibit low mammalian toxicity, especially when their surface contains anionic or neutral groups, such as carboxylic or hydroxylic functionalities. The physicochemical properties of these dendrimers are dependent on their shape and the charge density of their protonated primary amine groups on their surface. Together with high solubility in water, these characteristics have led to the use of these polyamines to mediate efcient DNA transfer into numerous cell lines in vitro (Kabanov and Kabanov, 1995; Bielinska et al., 1997, 1999; Delong et al., 1997; Kabanov et al., 1998; Abdelhady et al., 2003; Caminade, 2008). Also, it was found that the molecular exibility/rigidity of dendrimers plays a crucial role in the binding of the genetic materials, which was controlled by the modulation between the enthalpy and the entropy of binding. While exible dendrimers (G4) have demonstrated good adaptability to genetic materials, G6 has behaved like a rigid sphere with a consistent loss in the binding afnity, and G5 has shown a hybrid behavior with a strong dependence of its properties on
the pH (Pavan et al., 2010). Figure 77 shows the effect of the generation (exibility/rigidity) on the morphological behaviors of dendrimers when imaged by atomic force microscopy (AFM) at the water-mica interface following exposure of the mica surface to a 0.14 pg/mL or 2 µg/mL aqueous solution of G4 or G6, respectively. Figure 77a shows the adsorption of G4 onto mica. Globular aggregates of average height of 2.0 ± 0.6 nm and a diameter of 29.6 ± 3.3 nm were observed. Figure 77b shows the adsorption of G6 onto mica. Unlike the globular aggregates obtained for G4, individual features consistent with the dimensions of single G6 molecules were observed. Their mean diameters and height were 18 ± 5 nm and 2.1 ± 0.6 nm, respectively. The discrepancies observed are most likely reective of the rigidity of G6, which enable them to retain their shape on mica and appear as discrete molecules. The discrepancy in the measured diameters is most likely due to the Atomic Force microscopy tip convolution and sample compression effects.
