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

The document reviews advancements in smart nano-PROTACs for targeted protein degradation in cancer therapy, highlighting their potential to overcome limitations of traditional PROTACs, such as poor cell permeability and systemic toxicity. By integrating nanotechnology and stimuli-responsive elements, these systems enhance stability, delivery efficiency, and specificity, reducing off-target effects. Innovations include photocaged, enzyme-triggered, and radio-triggered nano-PROTACs, which allow precise spatiotemporal control of protein degradation. Notable developments like X-ray-responsive nanomicelles and ultrasound-activated nano-PROTACs show significant tumor inhibition in preclinical models. Despite challenges like limited tissue penetration, these strategies demonstrate promising therapeutic potential, with ongoing collaboration needed to translate them into effective cancer treatments.