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


Journal

Nature chemistry
ISSN: 1755-4349
Titre abrégé: Nat Chem
Pays: England
ID NLM: 101499734

Informations de publication

Date de publication:
07 2023
Historique:
received: 03 11 2021
accepted: 05 04 2023
medline: 7 7 2023
pubmed: 12 5 2023
entrez: 11 5 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 37169984
doi: 10.1038/s41557-023-01199-w
pii: 10.1038/s41557-023-01199-w
pmc: PMC10322715
doi:

Substances chimiques

Palladium 5TWQ1V240M
Antineoplastic Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

980-987

Informations de copyright

© 2023. The Author(s).

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Auteurs

Xue-Quan Zhou (XQ)

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, People's Republic of China.
Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Peiyuan Wang (P)

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, People's Republic of China.
Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, People's Republic of China.

Vadde Ramu (V)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.

Liyan Zhang (L)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.

Suhua Jiang (S)

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, People's Republic of China.
Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, People's Republic of China.

Xuezhao Li (X)

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, People's Republic of China.

Selda Abyar (S)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.

Panagiota Papadopoulou (P)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.

Yang Shao (Y)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.

Ludovic Bretin (L)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.

Maxime A Siegler (MA)

Department of Chemistry, Johns Hopkins University, Baltimore, MD, USA.

Francesco Buda (F)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.

Alexander Kros (A)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands.

Jiangli Fan (J)

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, People's Republic of China.

Xiaojun Peng (X)

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, People's Republic of China.

Wen Sun (W)

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, People's Republic of China. sunwen@dlut.edu.cn.

Sylvestre Bonnet (S)

Leiden Institute of Chemistry, Universiteit Leiden, Leiden, the Netherlands. bonnet@chem.leidenuniv.nl.

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Classifications MeSH