Abstract：
Antibody-drug conjugates (ADCs), which combine the precise targeting capabilities of antibodies with the powerful cytotoxicity of small-molecule drugs, have evolved into a promising approach for tumor treatment. However, the traditional covalent coupling method requires the design of a specific linker tailored to the properties of the small-molecule drugs, which greatly limits the development of ADCs and the range of drugs that can be used. Herein, a novel type of antibody-calixarene drug conjugates (ACDCs) that function similarly to ADCs by delivering drugs to their targets using antibodies but without the requirement of covalent conjugation of the drugs with antibodies is presented. By replacement of conventional linkers with supramolecular linkers, the ACDCs can load various chemotherapeutic drugs through host-guest interactions. Furthermore, ACDCs are readily reduced upon reaching the hypoxic microenvironment, resulting in rapid release of the drugs. With this precise drug encapsulation and controlled release mechanism, ACDCs deliver drugs to tumor tissues effectively and achieve a significantly enhanced antitumor effect. Considering that the ACDCs can be easily prepared by combining antibody-calixarene conjugates derived from tumor-targeting antibodies with various small-molecule drugs, ACDCs may provide a promising platform technology to accelerate ADC development and thus improve the therapeutic efficacy of chemotherapy.
摘要：
抗体-药物缀合物（ADC），它结合了抗体的精确靶向能力和小分子药物的强大细胞毒性，已经发展成为一种有希望的肿瘤治疗方法。然而,传统的共价偶联方法需要根据小分子药物的特性设计特定的接头，这极大地限制了ADC的发展和可以使用的药物范围。在这里，提出了一种新型的抗体-杯芳烃药物缀合物（ACDC），其通过使用抗体将药物递送到其靶标而功能类似于ADC，但不需要药物与抗体的共价缀合。通过用超分子接头代替常规接头，ACDC可以通过主客体相互作用负载各种化疗药物。此外，ACDC在到达低氧微环境时容易减少，导致药物的快速释放。凭借这种精确的药物封装和控释机制，ACDC将药物有效地递送至肿瘤组织并实现显著增强的抗肿瘤效果。考虑到ACDC可以通过将来自肿瘤靶向抗体的抗体-杯芳烃缀合物与各种小分子药物组合来容易地制备,ACDCs可能提供一种有前途的平台技术来加速ADC的发展，从而提高化疗的疗效。
