Macromolecule-drug conjugates (MDCs) occupy a critical niche in modern pharmaceuticals that deals with the assembly and combination of a macromolecular carrier, a drug cargo, and a linker toward the creation of effective therapeutics. Macromolecular carriers such as synthetic biocompatible polymers and proteins are often exploited for their inherent ability to improve drug circulation, prevent off-target drug cytotoxicity, and widen the therapeutic index of drugs. One of the most significant challenges in MDC design involves tuning their drug release kinetics to achieve high spatiotemporal precision. This level of control requires a thorough qualitative and quantitative understanding of the bond cleavage event. In this review, we highlight specific research findings that emphasize the importance of establishing a precise structure-function relationship for MDCs that can be used to predict their bond cleavage and drug release kinetic parameters. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 12 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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大分子-药物缀合物的键断裂和药物释放动力学的预测平台。

大分子药物偶联物（MDC）在现代药物中占据着至关重要的位置，该领域涉及大分子载体，药物货物和连接剂的组装和组合，以建立有效的治疗方法。诸如合成生物相容性聚合物和蛋白质之类的大分子载体由于其固有的改善药物循环，防止脱靶药物的细胞毒性和扩大药物治疗指数的固有能力而经常被开发利用。MDC设计中最重大的挑战之一是调整其药物释放动力学以实现高时空精度。这种控制水平要求对键断裂事件有彻底的定性和定量了解。在这篇评论中，我们重点介绍了一些具体的研究发现，这些发现强调了为MDC建立精确的结构-功能关系的重要性，该关系可用于预测其键断裂和药物释放动力学参数。《化学和生物分子工程年度评论》第12卷的最终最终在线发布日期为2021年6月。有关修订的估算，请参见http://www.annualreviews.org/page/journal/pubdates。