Department of Pharmacy, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Department of Otolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130021, China.
Int J Biol Macromol. 2024 Aug;275(Pt 1):133680. doi: 10.1016/j.ijbiomac.2024.133680. Epub 2024 Jul 4.
Proteolysis targeting chimeras (PROTACs) can use the intrinsic protein degradation system in cells to degrade pathogenic target proteins, and are currently a revolutionary frontier of development strategy for tumor treatment with small molecules. However, the poor water solubility, low cellular permeability, and off-target side effects of most PROTACs have prevented them from passing the preclinical research stage of drug development. This requires the use of appropriate delivery systems to overcome these challenging hurdles and ensure precise delivery of PROTACs towards the tumor site. Therefore, the combination of PROTACs and multifunctional delivery systems will open up new research directions for targeted degradation of tumor proteins. In this review, we systematically reviewed the design principles and the most recent advances of various PROTACs delivery systems. Moreover, the constructive strategies for developing multifunctional PROTACs delivery systems were proposed comprehensively. This review aims to deepen the understanding of PROTACs drugs and promote the further development of PROTACs delivery system.
蛋白水解靶向嵌合体（PROTACs）可以利用细胞内固有蛋白质降解系统来降解致病靶蛋白，目前是小分子肿瘤治疗发展策略的一个革命性前沿。然而，大多数 PROTACs 的水溶性差、细胞通透性低和脱靶副作用，阻止了它们通过药物开发的临床前研究阶段。这需要使用适当的递送系统来克服这些具有挑战性的障碍，并确保 PROTACs 精确递送到肿瘤部位。因此，PROTACs 和多功能递送系统的结合将为肿瘤蛋白的靶向降解开辟新的研究方向。在这篇综述中，我们系统地回顾了各种 PROTACs 递送系统的设计原则和最新进展。此外，还全面提出了开发多功能 PROTACs 递送系统的建设性策略。本综述旨在加深对 PROTACs 药物的理解，并促进 PROTACs 递送系统的进一步发展。
