One-Pot Synthesis of Dual-Responsive Hyperbranched Polymeric Prodrugs Using an All-in-One Chain Transfer Monomer

Over the past decades, tremendous progress has been advanced in the preparation of hyperbranched polymers (HPs), especially for the one-pot synthesis of segmented HPs by using self-condensing vinyl polymerization based on controlled living radical polymerization techniques. However, the fabrication of hyperbranched polymeric prodrugs (HPPs) still requires multistep postpolymerization conjugations, which generally suffer from low and uncontrolled conjugation efficacy of drug molecules due to the steric hindrance, low yields because of multistep synthesis, and scale-up difficulties attributed to batch-to-batch variations. To further address these issues and provide a highly straightforward and robust strategy toward HPPs, we reported in this study the one-pot preparation of dual-responsive hyperbranched polymeric prodrugs (DRHPPs) using an all-in-one chain transfer monomer that integrates a drug molecule with both acidic pH- and reduction-sensitive links. The resulting DRHPPs with precisely regulated drug loading content and great therapeutic efficacy offered a highly promising platform for efficient anticancer drug delivery.