Figure 7(a) shows an image of a DU145 prostate tumor in a nude mouse obtained with the system following intravenous administration

of PLGA NP (same NP as described in Figure4(b)). The system was capable of detecting the distribution of an unlabeled ultrasound contrast agent (UCA, VisualSonics) and allowed its visualization in the tumor (the areas with high concentration are represented in green). A specially developed computer code allowed to quantify kinetics of this UCA in the tumor (Figure 7(a), right panel). Inhibitors,research,lifescience,medical There was a sharp increase of the concentration in the whole tumor within first 2 to 3 seconds after the injection that was followed by a wash-out process (decrease of the contrast intensity). The necrotic Inhibitors,research,lifescience,medical areas

at the center of the tumor had similar kinetics but less concentration of the UCA due to lower vascularization (Figure 7(b), left panel). In contrast, injection of the PLGA nanoparticles into the same mouse (after clearance from the UCA) demonstrated almost constant concentration of the PLGA nanoparticles 15 seconds after the injection (Figure 7(b) -(2)). This effect resulted from competition of two processes: (1) the Inhibitors,research,lifescience,medical decrease of nanoparticles concentration in blood and (2) the increase of their concentration in the tumor blood vessels due to the EPR effect. Moreover, the contrast intensity MG-132 mouse produced by the PLGA nanoparticles (~175) was much higher compared to that of the UCA (~100). These data indicate Inhibitors,research,lifescience,medical that high-resolution ultrasound small animals imaging systems are able to detect the PLGA nanoparticles in tumors in vivo and that these nanoparticles are highly echogenic. Figure 7 Inhibitors,research,lifescience,medical . Echogenic PLGA nanoparticles can be utilized also as ultrasound contrast agents in vivo. (a) (1) A tumor image obtained with the high-resolution ultrasound system VEVO770 (VisualSonics). (2) Kinetics of the contrast agent in the whole tumor shown in … Further modifications can be made to echogenic PLGA NP to enhance their

potential for longer circulation half-life and for enabling tumor-specific targeting. For example, surface modifications can be made to polymeric nanoparticles to add PEGylated phospholipids in order to escape GPX6 recognition and clearance by the mononuclear phagocyte system and achieve passive tumor targeting. Nanoparticles consisting of a shell of PLGA encapsulating a liquid core of perfluorooctyl bromide (PFOB) can be decorated with poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) and resulting particles still are echogenic and can allow visualization of MIA-PaCa-2 pancreatic tumors in vivo, following intratumoral or intravenous injection (Figure 8(a)). In this example, the tumor was visualized only following intratumoral UCA injection.