ROS-Responsive Polymeric Nanocarriers with Photoinduced Exposure of Cell-Penetrating Moieties for Specific Intracellular Drug Delivery

In situ modulation of the surface properties on the micellar drug delivery nanocarriers offer an efficient method to improve the drug delivery efficiency into cells while maintaining stealth and stability during blood circulation. Light has been demonstrated to be a temporally and spatially controllable tool to improve cellular internalization of nanoparticles. Herein, we develop reactive oxygen species (ROS)-responsive mixed polymeric micelles with photoinduced exposure of cell-penetrating moieties via photodynamic ROS production, which can facilitate cellular internalization of paclitaxel (PTX) and chlorin e6 (Ce6)-coloaded micelles for synergistic effect of photodynamic and chemo-therapy. The thioketal bonds-linked block polymers poly(e-caprolactone)-TL-poly(N, N-dimethylacrylamide) (PCL-TL-PDMA) with a long PDMA block are used to self-assemble into mixed micelles with PCL-b-poly(2-guanidinoethyl methacrylate) (PCL-PGEMA) consisting of a short PGEMA block, which are further used to coencapsulate PTX an...