Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, 637457, Singapore.
ACS Nano. 2024 Oct 22;18(42):28502-28530. doi: 10.1021/acsnano.4c09800. Epub 2024 Oct 8.
Proteolysis targeting chimeras (PROTACs) represent a transformative class of therapeutic agents that leverage the intrinsic protein degradation machinery to modulate the hemostasis of key disease-associated proteins selectively. Although several PROTACs have been approved for clinical application, suboptimal therapeutic efficacy and potential adverse side effects remain challenging. Benefiting from the enhanced targeted delivery, reduced systemic toxicity, and improved bioavailability, nanomedicines can be tailored with precision to integrate with PROTACs which hold significant potential to facilitate PROTAC nanomedicines (nano-PROTACs) for clinical translation with enhanced efficacy and reduced side effects. In this review, we provide an overview of the recent progress in the convergence of nanotechnology with PROTAC design, leveraging the inherent properties of nanomaterials, such as lipids, polymers, inorganic nanoparticles, nanohydrogels, proteins, and nucleic acids, for precise PROTAC delivery. Additionally, we discuss the various categories of PROTAC targets and provide insights into their clinical translational potential, alongside the challenges that need to be addressed.
蛋白水解靶向嵌合体（PROTACs）代表了一类具有变革性的治疗药物，利用内在的蛋白质降解机制有选择性地调节关键疾病相关蛋白的止血作用。尽管已经有几种 PROTACs 被批准用于临床应用，但治疗效果不理想和潜在的不良反应仍然是具有挑战性的。受益于增强的靶向递送、降低的系统毒性和改善的生物利用度，纳米药物可以精确地与 PROTAC 结合，这对于促进 PROTAC 纳米药物（nano-PROTACs）的临床转化具有重要意义，可以提高疗效和降低副作用。在这篇综述中，我们概述了纳米技术与 PROTAC 设计的融合的最新进展，利用纳米材料的固有特性，如脂质、聚合物、无机纳米粒子、纳米水凝胶、蛋白质和核酸，实现精确的 PROTAC 递送。此外，我们讨论了各种 PROTAC 靶标的类别，并提供了对其临床转化潜力的见解，以及需要解决的挑战。
