Upon immobilization, dendrimers deform and adopt elliptical cap geometry. Upon uptake of indomethacin, STM imaging reveals that G4 PAMAM-OH-(Pt2+)n-(Indo)m dendrimers are taller than the bare G4 dendrimers. Figure2(a) is a 20 × 20nm2 STM topograph of G4 PAMAM-OH-(Pt2+)n-(Indo)m dendrimers immobilized on a Au(111) surface. The bright protrusions correspond to individual G4 PAMAM-OH-(Pt2+)n-(Indo)m dendrimer molecules. The STM apparent height, or hAPP, is obtained by measuring the height from the lowest point in the immediate surrounding
matrix to the top of the dendrimer. Inhibitors,research,lifescience,medical These cursors indicate that dendrimers loaded with despite indomethacin adopt an elliptical dome shape similar to the base dendrimers reported previously [28, 29, 47, 48]. The hAPP in cursor profiles 1 and 2 is 0.43 and 0.48nm, respectively. In contrast, Inhibitors,research,lifescience,medical the hAPP of a typical G4 dendrimer, as shown in Figure2(a), measures 0.35nm and 0.33nm, respectively. The uptake of indomethacin increases the hAPP by 0.08nm. Among the 102 dendrimers we compared, drug-loaded G4 dendrimers appear 0.09 ± 0.02nm taller than the dendrimers themselves. Inhibitors,research,lifescience,medical The true height is further investigated using AFM as described in the previous section. The typical real height (hREAL) for G4 and indo-G4 complexes are 2.5 ± 0.3nm and 3.4 ± 0.7nm, respectively. Figure
2 STM and AFM topographic lateral and height measurements determine the volume of single G4 PAMAM-OH-(Pt2+)n-(Indo)m Inhibitors,research,lifescience,medical and G4 PAMAM-OH-(Pt2+)n dendrimers. (a) A 20 × 20nm2 STM topograph of G4 PAMAM-OH-(Pt2+)n-(Indo)m dendrimers immobilized … After measuring the lateral and vertical dimensions, the volume of dendrimers can be accurately determined and compared. Assuming an elliptical cap Volasertib leukemia geometry for all dendrimers, the volume of individual Inhibitors,research,lifescience,medical molecules may be calculated using V = (1/6πhREAL)(3/4ab + hREAL2), where a and b are the long and short lateral axes, respectively. In a typical case shown in
Figure 2, the lateral dimensions are Carfilzomib a = 5.6nm, b = 4.2nm for the indomethacin-loaded G4 and the height is 3.4nm, thus V = 52.3nm3. From Figure2(b), the bare G4 dendrimers measure a = 5.7nm, b = 5.2nm, and hREAL = 2.2nm, which corresponds to a V = 31.2nm3. Among the 102 dendrimers compared, drug-loaded dendrimers are 54% more voluminous than base dendrimers. The average lateral dimensions are a = 6.8 ± 1.2nm and b = 5.6 ± 0.9nm for indomethacin-loaded G4 and a = 6.2 ± 0.8nm and b = 5.1 ± 0.7nm for unloaded G4. Since the lateral deformation of both loaded and unloaded G4 dendrimers are similar, the height, and thus volume, increases observed with the addition of indomethacin suggest that the addition of indomethacin to the exterior of dendrimers increases the overall structural integrity upon surface immobilization. 3.6.
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