Self-assembling molecular drugs combine the easy preparation typical of small-molecule chemotherapy and the tumour-targeting properties of drug–nanoparticle conjugates. However, they require a supramolecular interaction that survives the complex environment of a living animal. Here we report that the metallophilic interaction between cyclometalated palladium complexes generates supramolecular nanostructures in living mice that have a long circulation time (over 12 h) and efficient tumour accumulation rate (up to 10.2% of the injected dose per gram) in a skin melanoma tumour model. Green light activation leads to efficient tumour destruction due to the type I photodynamic effect generated by the self-assembled palladium complexes, as demonstrated in vitro by an up to 96-fold cytotoxicity increase upon irradiation. This work demonstrates that metallophilic interactions are well suited to generating stable supramolecular nanotherapeutics in vivo with exceptional tumour-targeting properties.

自组装分子药物结合了小分子化疗典型的易于制备和药物-纳米颗粒缀合物的肿瘤靶向特性。然而，它们需要超分子相互作用才能在活体动物的复杂环境中生存。在这里，我们报道了环金属化钯配合物之间的亲金属相互作用在活体小鼠体内产生超分子纳米结构，这些结构在皮肤黑色素瘤中具有较长的循环时间（超过12小时）和有效的肿瘤积累率（高达每克注射剂量的10.2%）模型。由于自组装钯配合物产生的 I 型光动力效应，绿光激活可有效破坏肿瘤，体外照射后细胞毒性增加高达 96 倍。