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Zhou, X.; Wang, P.; Vadde, R.; Zhang, L.; Jiang, S.; Li, X.; ... ; Bonnet, S.A. (2023)

In vivo metallophilic self-assembly of a light-activated anticancer drug

Article / Letter to editor
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...Show moreSelf-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.Show less
All authors
Zhou, X.; Wang, P.; Vadde, R.; Zhang, L.; Jiang, S.; Li, X.; Abyar, S.; Papadopoulou, P.; Shao, Y.; BRETIN, L.R.; Siegler, M.A.; Buda, F.; Kros, A.; Fan, J.; Peng, X.; Sun, W.; Bonnet, S.A.
Date
2023-05-11
Journal
Nature Chemistry
Volume
15
DOI
doi:10.1038/s41557-023-01199-w