Fig. 8

Chemical Structure of the Dual pH-Responsive Polymer. Doxorubicin (DOX) Conjugate (PPC-Hyd-DOX-DA) and Schematic Illustration of Its pH Triggered Cellular Internalization and Intracellular Drug Release (Panel A). Time-dependent sphere formation of SK-3rd cells after incubation with various formulations (a and c) and the relative cell numbers/sphere measured at 14 days (b and d). Cells were first incubated with the formulations in culture media for 2 h at pH 7.4 (a and b) or 6.8 (c and d), and then the media were replaced with fresh media and further incubated at pH 7.4. p < 0.005. PBS control was set as 100%. The dose of DOX or its equivalent was 2 μg/mL (Panel B). (a) Cellular uptake of PPC-Hyd-DOX-DA NPs (red) at pH 6.8 or 7.4 after incubation with MDA-MB-231 cells for 1 h. DAPI (40, 6-diamidino-2 phenylindole, blue) and Alexa Fluor488 phalloidin (green) were used to stain cell nuclei and F-actin, respectively. (b) Subcellular distribution of PPC-Hyd-DOX-DA NPs (red) at pH 6.8. DAPI (blue) and Lysotracker Green (green) were used to stain the cell nuclei and acidic organelles. Cells were imaged using a 60 water-immersion objective (Panel C). Reprinted with permission from Journal of American Chemical Society,