这篇综述强调了配备基于金属和自然启发的有效载荷的抗体-药物缀合物(ADC)的重大进展,专注于抗体缀合的合成策略。传统方法如马来酰亚胺和琥珀酰亚胺缀合和经典缩合反应对于金属药物和天然化合物是普遍的。然而,新兴的非传统策略,如光共轭,由于其温和的条件,正在获得牵引力,在减少副反应的方面,ADC的选择性形成。这篇综述还总结了这些ADC的治疗和诊断特性,与非结合的有效载荷相比,突出了它们在癌症治疗中增强的选择性和减少的副作用。ADC将单克隆抗体的特异性与化疗药物的细胞毒性相结合,提供了一种有针对性的方法来消除癌细胞,同时保留健康组织。这种靶向机制在各种恶性肿瘤中显示出令人印象深刻的临床疗效。未来的关键进展包括改进的接头技术,以增强细胞毒性剂的稳定性和受控释放,合并小说,更有效,细胞毒性剂,以及通过基因组和蛋白质组学技术鉴定新的癌症特异性抗原。ADC也有望在与免疫检查点抑制剂的联合治疗中发挥关键作用。CAR-T细胞,和小分子抑制剂,导致更持久和潜在的治愈结果。正在进行的研究和临床试验正在扩大他们的能力,为更有效铺平道路,更安全,和个性化治疗,将ADC定位为现代医学的基石,为患者提供新的希望。
This review highlights significant advancements in antibody-drug conjugates (ADCs) equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for
metallodrugs and natural compounds. However, emerging non-conventional strategies such as photoconjugation are gaining traction due to their milder conditions and, in an aspect which minimizes side reactions, selective formation of ADC. The review also summarizes the therapeutic and diagnostic properties of these ADCs, highlighting their enhanced selectivity and reduced side effects in cancer treatment compared to non-conjugated payloads. ADCs combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy drugs, offering a targeted approach to the elimination of cancer cells while sparing healthy tissues. This targeted mechanism has demonstrated impressive clinical efficacy in various malignancies. Key future advancements include improved linker technology for enhanced stability and controlled release of cytotoxic agents, incorporation of novel, more potent, cytotoxic agents, and the identification of new cancer-specific antigens through genomic and proteomic technologies. ADCs are also expected to play a crucial role in combination therapies with immune checkpoint inhibitors, CAR-T cells, and small molecule inhibitors, leading to more durable and potentially curative outcomes. Ongoing research and clinical trials are expanding their capabilities, paving the way for more effective, safer, and personalized treatments, positioning ADCs as a cornerstone of modern medicine and offering new hope to patients.