Light-Responsive Prodrug-Based Supramolecular Nanosystems for Site-Specific Combination Therapy of Cancer

On-demand release of chemotherapeutic drugs from their prodrugs triggered by light irradiation has been attracting great attention for effective cancer treatment. Herein, we prepared prodrug-based supramolecular nanoparticles (HA–aPS–aCPT) composed of (1) β-cyclodextrin conjugated hyaluronic acid polymer (HA–CD), (2) adamantane-modified camptothecin prodrug (aCPT) caged via reactive oxygen species (ROS) responsive thioketal linker, and (3) adamantane-modified photosensitizer (aPS), for combination photodynamic therapy and light-controlled chemotherapy. aCPT could release free camptothecin by the cleavage of ROS-sensitive thioketal linker. aPS is employed to produce ROS under light irradiation. HA–aPS–aCPT nanoparticles are formed by supramolecular means with excellent colloidal stability and monodispersity in aqueous solution. Confocal imaging and flow cytometric analysis confirm the selective uptake of HA–aPS–aCPT nanoparticles via CD44 receptor-mediated endocytosis by MDA-MB-231 cells, on account of the...