A click-reaction for precise combination drug delivery: a general pH-responsive degradable backboned polyprodrug strategy†

Abstract

A novel microenvironment-responsive drug co-delivery system leverages acylalkynyl–hydroxyl click polymerization to incorporate diverse drug molecules with hydroxyl groups. This innovative polyprodrug approach enables precise drug grafting and selective tumor microenvironment degradation, facilitating targeted combination therapy. By successfully synthesizing dual-drug polyprodrugs with demonstrated tumor cell-killing potential and minimal normal cell damage, the method provides a promising platform for personalized, synergistic therapeutic strategies.