Dynamic supramolecular self-assembly of platinum(ii) complexes perturbs an autophagy–lysosomal system and triggers cancer cell death. Issue 46 (29th September 2021)

• Record Type: Journal Article
• Authors: Tong, Ka-Chung; Wan, Pui-Ki; Lok, Chun-Nam; Che, Chi-Ming
• Is Part Of: Chemical science. Volume 12:Issue 46(2021)
• Page Start: 15229
• Page End: 15238
• Publication Date: 2021-09-29
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1sc02841c
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Self-assembly of platinum(ii ) glycosylated arylacetylide gave transformable superstructures upon enzymatic action in cellulo, leading to perturbation of an autophagy-lysosomal system and 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CArOGlu)](CF3 SO3 ) (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.