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PH-Driven Intracellular Nano-to-Molecular Disassembly of Heterometallic [AuL]{ReQ} Colloids (L = PNNP Ligand; Q = S or Se)

Abstract

The present work introduces a simple, electrostatically driven approach to engineered nanomaterial built from the highly cytotoxic [AuL] complex (Au, L = 1,5-bis(p-tolyl)-3,7-bis(pyridine-2-yl)-1,5-diaza-3,7-diphosphacyclooctane (PNNP) ligand) and the pH-sensitive red-emitting [{ReQ}(OH)] (Re-Q, Q = S or Se) cluster units. The protonation/deprotonation of the Re-Q unit is a prerequisite for the pH-triggered assembly of Au and Re-Q into AuRe-Q colloids, exhibiting disassembly in acidic (pH = 4.5) conditions modeling a lysosomal environment. The counter-ion effect of polyethylenimine causes the release of Re-Q units from the colloids, while the binding with lysozyme restricts their protonation in acidified conditions. The enhanced luminescence response of Re-S on the disassembly of AuRe-S colloids in the lysosomal environment allows us to determine their high lysosomal localization extent through the colocalization assay, while the low luminescence of Re-Se units in the same conditions allows us to reveal the rapture of the lysosomal membrane through the use of the Acridine Orange assay. The lysosomal pathway of the colloids, followed by their endo/lysosomal escape, correlates with their cytotoxicity being on the same level as that of Au complexes, but the contribution of the apoptotic pathway differentiates the cytotoxic effect of the colloids from that of the Au complex arisen from the necrotic processes.

Citing Articles

Luminescent Gold Nanoclusters for Bioimaging: Increasing the Ligand Complexity.

Mordini D, Mavridi-Printezi A, Menichetti A, Cantelli A, Li X, Montalti M Nanomaterials (Basel). 2023; 13(4).

PMID: 36839016 PMC: 9960743. DOI: 10.3390/nano13040648.

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