用于药物递送的酸可降解和酶可裂解连接子的进展。
Advances in acid-degradable and enzyme-cleavable linkers for drug delivery.
作者信息
Zhao Sheng, Yu Na, Han Hesong, Guo Shutao, Murthy Niren
机构信息
Department of Bioengineering and Innovative Genomics Institute, University of California Berkeley, 2151 Berkeley Way, Berkeley, CA 94720, USA.
Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071, China.
出版信息
Curr Opin Chem Biol. 2025 Feb;84:102552. doi: 10.1016/j.cbpa.2024.102552. Epub 2024 Dec 5.
Drug delivery vectors have the potential to improve the efficacy of therapeutics, including small molecules and nucleic acid-based drugs. However, challenges remain in developing linkages that enable the precise and efficient release of therapeutic cargo in response to mildly acidic environments or lysosomal enzymes. This review highlights recent advances in acid-degradable acetal/ketal and enzyme-cleavable linkages for endolysosomal release. These innovations include the developments of azido-acetal linkers with improved stability and hydrolysis kinetics, organocatalytic trans-isopropenylation for synthesizing asymmetric ketals and their applications in drug delivery, and enzyme-cleavable linkers activated by cathepsin B or β-galactosidase.
药物递送载体有潜力提高治疗药物的疗效，包括小分子药物和基于核酸的药物。然而，在开发能够响应轻度酸性环境或溶酶体酶而实现治疗性有效载荷精确且高效释放的连接物方面，仍然存在挑战。本综述重点介绍了用于内溶酶体释放的酸可降解缩醛/缩酮和酶可裂解连接物的最新进展。这些创新包括具有改善的稳定性和水解动力学的叠氮基缩醛连接子的开发、用于合成不对称缩酮的有机催化反式异丙烯基化及其在药物递送中的应用，以及由组织蛋白酶B或β-半乳糖苷酶激活的酶可裂解连接子。
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