Emerging Strategies in Smart Nano-PROTAC for Stimuli-Responsive Protein Degradation and Precision Cancer Therapy

Proteolysis-targeting chimeras (PROTACs) are a promising strategy for targeted protein degradation, offering advantages like catalytic efficiency and high specificity. Despite the progress of PROTACs such as ARV-471 and CC-94676 into Phase III clinical trials, challenges like poor cell permeability and systemic off-target effects remain. To overcome these, stimulus-responsive nanoparticle-based PROTACs (nano-PROTACs) have been developed, utilizing stimuli like redox status and light for precise activation. These smart nano-PROTACs enhance specificity and controllability, improving therapeutic efficacy and minimizing toxicity, thus paving the way for next-generation degraders with better pharmacological properties.