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, and knowledge of the interaction of MCgs with biological targets is still lacking. In this context, this work reports on the integration of a gold(III) porphyrin scaffold into a prismatic metallacage structure and explores its application for multimodal therapy of cancer in vitro, namely enabling both photodynamic therapy (PDT) and chemotherapy activity. Combining experimental approaches with a state-of-the-art metadynamics (MetaD) theoretical study, we discovered that the gold cage shows unprecedented host-guest interactiondriven selective stabilization of guanine-quadruplexes (G4) structures - validated anticancer drug targets - disclosing a new mechanism to pursue in the design of supramolecular drugs.

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中文翻译：

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多功能卟啉金属包体设计的点睛之笔：药物-靶标相互作用的主客体化学。

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，复杂性和功能性更高的MCgs的合成是一个巨大的挑战，并且对于MCgs与生物靶点相互作用的了解仍然缺乏。在此背景下，这项工作报告了将金（III）卟啉支架整合到棱柱金属笼结构中，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（PDT）和化疗活性。将实验方法与最先进的元动力学 (MetaD) 理论研究相结合，我们发现金笼显示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标——揭示了一种新的超分子药物设计中要追求的机制。

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