PH-Activatable engineered nanoparticle-based selective hexokinase 2 degrader provokes GSDME-dependent pyroptosis for cancer therapy.

ABSTRACT: Proteolysis targeting chimeras (PROTACs) technology has been developed as an exquisite promising approach for targeted protein degradation by hijacking the cellular ubiquitin-proteasome system (UPS). However, traditional PROTACs often suffer from insufficient tumor accumulation, unfavorable membrane penetration, and always-on biological activity, limiting their antitumor performance. Herein, we report a novel pH-activatable engineered nanoparticle-based selective hexokinase 2 degrader (Nano-PROTACs) for cancer therapy. Nano-PROTACs were constructed by conjugating PEI-based PROTACs to amphiphilic nanoparticles via acid-detachable cis-aconitic anhydride (CAA) bonds. Then, Nano-PROTACs allowed PEI-based PROTACs release within the tumor acidic microenvironment, which bounded to H

SUBMITTER: Gong L 

PROVIDER: S-EPMC12828081 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature