Issue 46, 2021

Dynamic supramolecular self-assembly of platinum(ii) complexes perturbs an autophagy–lysosomal system and triggers cancer cell death

Abstract

Self-assembly of platinum(II) complexes to form supramolecular structures/nanostructures due to intermolecular ligand π–π stacking and metal–ligand dispersive interactions is widely used to develop functional molecular materials, but the application of such non-covalent molecular interactions has scarcely been explored in medical science. Herein is described the unprecedented biological properties of platinum(II) complexes relevant to induction of cancer cell death via manifesting such intermolecular interactions. With conjugation of a glucose moiety to the planar platinum(II) terpyridyl scaffold, the water-soluble complex [Pt(tpy)(C[triple bond, length as m-dash]CArOGlu)](CF3SO3) (1a, tpy = 2,2′:6′,2′′-terpyridine, Glu = glucose) is able to self-assemble into about 100 nm nanoparticles in physiological medium, be taken up by lung cancer cells via energy-dependent endocytosis, and eventually transform into other superstructures distributed in endosomal/lysosomal and mitochondrial compartments apparently following cleavage of the glycosidic linkage. Accompanying the formation of platinum-containing superstructures are increased autophagic vacuole formation, lysosomal membrane permeabilization, and mitochondrial membrane depolarization, as well as anti-tumor activity of 1a in a mouse xenograft model. These findings highlight the dynamic, multi-stage extracellular and intracellular supramolecular self-assembly of planar platinum(II) complexes driven by modular intermolecular interactions with potential anti-cancer application.

Graphical abstract: Dynamic supramolecular self-assembly of platinum(ii) complexes perturbs an autophagy–lysosomal system and triggers cancer cell death

Supplementary files

Article information

Article type
Edge Article
Submitted
26 May 2021
Accepted
17 Sep 2021
First published
29 Sep 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 15229-15238

Dynamic supramolecular self-assembly of platinum(II) complexes perturbs an autophagy–lysosomal system and triggers cancer cell death

K. Tong, P. Wan, C. Lok and C. Che, Chem. Sci., 2021, 12, 15229 DOI: 10.1039/D1SC02841C

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