Photo‐Triggered ROS‐Responsive Supramolecular Nanoprodrugs for Targeted and Synergistic Chemo/Photodynamic/Gas Therapy

Photo-triggered ROS-responsive supramolecular nanoprodrugs (BNN6@GBTC NPs) are constructed via supramolecular self-assembly of amphiphilic prodrug molecule (GBTC) and NO donor (BNN6). BNN6@GBTC NPs possess good stability, ROS responsiveness, and selective HepG2 cells targetability via overexpressed galactose receptors on the cell membrane. When BNN6@GBTC NPs are taken up by HepG2 cells, they can generate ROS upon light irradiation, which can not only be used for photodynamic therapy, but also cleave the thioketal linkage to release camptothecin for chemotherapy. Meanwhile, BNN6 triggering release NO for gas therapy. BNN6@GBTC NPs enable targeted and synergistic chemo/photodynamic/gas therapy, which results in reduced damage to normal cells and enhanced anti-cancer efficacy in vitro. This work provides a novel approach for the design of nanoprodrugs based on supramolecular self-assembly to achieve the multimodal synergistic anti-cancer therapy.