Glutathione-Scavenging Nanoparticle-Mediated PROTACs Delivery for Targeted Protein Degradation and Amplified Antitumor Effects.

ABSTRACT: PROteolysis TArgeting Chimeras (PROTACs) are an emerging class of promising therapeutic modalities that selectively degrade intracellular proteins of interest by hijacking the ubiquitin-proteasome system. However, the lack of techniques to efficiently transport these degraders to targeted cells and consequently the potential toxicity of PROTACs limit their clinical applications. Here, a strategy of nanoengineered PROTACs, that is, Nano-PROTACs, is reported, which improves the bioavailability of PROTACs and maximizes their capacity to therapeutically degrade intracellular oncogenic proteins for tumor therapy. The Nano-PROTACs are developed by encapsulating PROTACs in glutathione (GSH)-responsive poly(disulfide amide) polymeric (PDSA) nanoparticles and show that ARV@PDSA Nano-PROTAC, nanoeng

SUBMITTER: Liu HJ 

PROVIDER: S-EPMC10238184 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature