The use of three-dimensional self-assembled metallacages (MCgs) as multimodal drug platforms holds great promise. However, the synthesis of MCgs with increased complexity and functionality is a great challenge since understanding of the interaction of MCgs with biological targets is still limited. In this context, this work reports on the integration of a gold(III) porphyrin scaffold into a prismatic MCg structure and explores its application for multimodal therapy of cancer in vitro, namely enabling both photodynamic therapy and chemotherapy. Combining experimental approaches with a state-of-the-art metadynamics theoretical study, we discovered that the gold cage shows unprecedented host–guest interaction-driven selective stabilization of guanine-quadruplex (G4) structures – validated anticancer drug targets – disclosing a new mechanism to pursue in the design of supramolecular drugs.

使用三维自组装金属笼（MCgs）作为多模式药物平台具有广阔的前景。然而，由于对 MCgs 与生物靶标相互作用的了解仍然有限，合成具有更高复杂性和功能的 MCgs 是一个巨大的挑战。在此背景下，这项工作报告了将金（III）卟啉支架整合到棱柱状 MCg 结构中，并探索其在体外癌症多模式治疗中的应用，即实现光动力疗法和化疗。将实验方法与最先进的元动力学理论研究相结合，我们发现金笼表现出前所未有的主客体相互作用驱动的鸟嘌呤四联体（G4）结构的选择性稳定——经过验证的抗癌药物靶点——揭示了一种新机制致力于超分子药物的设计。