Reductively activated CPP–PROTAC nanocomplexes enhance target degradation via efficient cellular uptake

Abstract

We developed a nanoparticle based on a cell-penetrating peptide-PROTAC conjugate with a disulfide linker, MZ1-R9, and dextran sulfate, enhancing cellular uptake and BRD4 degradation. This delivery platform significantly improves PROTAC bioavailability and offers a promising strategy to overcome membrane permeability challenges for targeted protein degradation.