靶向递送蛋白水解靶向嵌合体在癌症治疗中的研究进展

Advances in targeted delivery of proteolysis targeting chimeras in cancer therapy

摘要:

小分子抗癌药物通过靶向特定蛋白来抑制肿瘤生长，但大部分致病蛋白被认为是“不可成药”的。蛋白水解靶向嵌合体(proteolysis targeting chimeras, PROTAC)通过靶向降解目标蛋白来抑制肿瘤细胞生长，是一项非常有潜力的新技术。本文在介绍传统多肽型PROTAC和小分子型PROTAC基础上，详细总结了靶向递送型PROTAC的最新研究进展，主要包括识别分子介导靶向PROTAC、纳米材料介导靶向PROTAC和可控激活小分子PROTAC前药。研究表明，靶向递送型PROTAC在提高肿瘤细胞特异性、减少脱靶效应和降低生物毒性等方面具有潜在应用价值。最后，本文对PROTAC的成药性进行了展望。

Abstract:

Small-molecule anticancer drugs inhibited tumor growth based on targeted inhibition of specific proteins, while most of oncogenic proteins are “undruggable”. Proteolysis targeting chimeras (PROTAC) is an attractive and general strategy for treating cancer based on targeted degradation of oncogenic proteins. This review briefly describes the peptide-based PTOTAC and small molecule-based PROTAC. Subsequently, we summarize the development of targeted delivery of PROTAC, such as targeting molecule-mediated targeted delivery of PROTAC, nanomaterial-mediated targeted delivery of PROTAC and controllable activation of small-molecular PROTAC prodrug. Such strategies show potential application in improving tumor selectivity, overcoming off-target effect and reducing biotoxicity. At the end, the druggability of PROTAC is prospected.