Nanoplatform-Based Delivery Systems for PROTACs

Proteolysis Targeting Chimera (PROTAC) is a bifunctional small molecule composed of a ligand for the target protein, a ligand for an E3 ubiquitin ligase, and a chemical linker. It induces the formation of a ternary complex between the target protein and the E3 ligase, thereby promoting ubiquitination and subsequent proteasomal degradation of the target. As an emerging targeted protein degradation (TPD) strategy, PROTACs offer notable advantages such as rapid action, sustained efficacy, and high selectivity. However, PROTACs encounter significant challenges in in vivo delivery due to their unfavorable physicochemical properties, including high molecular weight, limited membrane permeability, and poor plasma stability. In recent years, the development of nanodelivery platforms has emerged as a promising strategy to overcome these limitations, significantly enhancing the bioavailability and therapeutic efficiency of PROTACs while accelerating their clinical translation and application.