Page - (000387) - in Biomedical Chemistry: Current Trends and Developments

hydrophobicity/hydrophilicity, and the interaction of nanoparticle with the plasma proteins and cell-surface receptors (Bachmann, 2010). It has been reported that nanoparticles with a size smaller than 500 nm are taken-up more efficiently by the DCs (Foged, 2005). In addition, a pre- clinical study performed in mice suggested that the nanoparticle size of 40–50 nm was optimal for nanovaccines (Fifis, 2004). However, nanoparticles up to 300 nm have already demonstrated effective induction of the CD4+ and CD8+ T cell responses (Fifis, 2004; Kasturi, 2011; Reichert, 2011; Shima, 2013; Tomic, 2014). Positively charged particles are taken-up more efficiently than those with a negative or neutral charge by the DCs in vitro (Foged, 2005). However, some in vivo studies have revealed no significant difference in the immunostimulatory effect between positively and negatively charged particles (Yotsumoto, 2004). Some studies have also shown that the particles with positive surface charge can immobilize the nanovaccines in negatively charged components presented in the extracellular matrix of the cells through electrostatic interactions (van den Berg, 2010), resulting in the inhibition of the immunostimulative responses, owing to the reduced tissue penetration. Figure 3.5.11: Confocal microscopy imaging of the PLGA nanoparticles in human DCs. (A) 4′,6- Diamidino-2-phenylindole channel. (B) Fluorescein isothiocyanate channel. (C) 4′,6-Diamidino-2- phenylindole and fluorescein isothiocyanate channels overlaid. (D) 4′,6-Diamidino-2- phenylindole, fluorescein isothiocyanate, and reflection channels overlaid. Reprinted with permission from (Ma, 2012).