Abstract：
A multivalent ligand delivery system holds tremendous potential in the field of tumor-targeted drug delivery. It addresses the challenges posed by the low affinity between small molecule ligand receptors and the rapid metabolism of small molecule drug conjugates (SMDCs) in vivo. Notably, existing multivalent ligand systems have demonstrated significant anti-tumor activity in various tumor models. In this study, we have developed a novel multivalent ligand delivery system for SN38, utilizing acetazolamide, a carbonic anhydrase IX (CA IX) inhibitor, as the target ligand. Our multivalent ligand delivery systems exhibited superior metabolic stability and enhanced targeting specificity compared to SMDC molecules. Furthermore, they demonstrated improved anti-proliferation activity, addressing the existing challenges associated with the low receptor affinity and rapid metabolism of SMDCs.
摘要：
多价配体递送系统在肿瘤靶向药物递送领域具有巨大潜力。它解决了小分子配体受体之间的低亲和力和小分子药物缀合物(SMDC)在体内的快速代谢带来的挑战。值得注意的是,现有的多价配体系统已经在各种肿瘤模型中证明了显著的抗肿瘤活性。在这项研究中,我们已经开发了一种新的多价配体递送系统SN38，利用乙酰唑胺，碳酸酐酶IX（CAIX）抑制剂，作为目标配体。与SMDC分子相比,我们的多价配体递送系统表现出优异的代谢稳定性和增强的靶向特异性。此外，它们表现出改进的防扩散活性，解决与SMDC的低受体亲和力和快速代谢相关的现有挑战。
