pH-Driven Intracellular Nano-to-Molecular Disassembly of Heterometallic [Au<sub>2</sub>L<sub>2</sub>]{Re<sub>6</sub>Q<sub>8</sub>} Colloids (L = PNNP Ligand; Q = S<sup>2−</sup> or Se<sup>2−</sup>)
Bulat Faizullin,
Irina Dayanova,
Igor Strelnik,
Kirill Kholin,
Irek Nizameev,
Aidar Gubaidullin,
Alexandra Voloshina,
Tatiana Gerasimova,
Ilya Kashnik,
Konstantin Brylev,
Guzel Sibgatullina,
Dmitry Samigullin,
Konstantin Petrov,
Elvira Musina,
Andrey Karasik,
Asiya Mustafina
Affiliations
Bulat Faizullin
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Irina Dayanova
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Igor Strelnik
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Kirill Kholin
Department of Nanotechnology in Electronics, Kazan National Research Technical University Named after A.N. Tupolev-KAI, 10 K. Marx Street, 420111 Kazan, Russia
Irek Nizameev
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Aidar Gubaidullin
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Alexandra Voloshina
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Tatiana Gerasimova
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Ilya Kashnik
Nikolaev Institute of Inorganic Chemistry, SB RAS, 3 Academician Lavrentiev Avenue, 630090 Novosibirsk, Russia
Konstantin Brylev
Nikolaev Institute of Inorganic Chemistry, SB RAS, 3 Academician Lavrentiev Avenue, 630090 Novosibirsk, Russia
Guzel Sibgatullina
Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevski Street, 420111 Kazan, Russia
Dmitry Samigullin
Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevski Street, 420111 Kazan, Russia
Konstantin Petrov
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Elvira Musina
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Andrey Karasik
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
Asiya Mustafina
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Street, 420088 Kazan, Russia
The present work introduces a simple, electrostatically driven approach to engineered nanomaterial built from the highly cytotoxic [Au2L2]2+ complex (Au2, 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 [{Re6Q8}(OH)6]4− (Re6-Q, Q = S2− or Se2−) cluster units. The protonation/deprotonation of the Re6-Q unit is a prerequisite for the pH-triggered assembly of Au2 and Re6-Q into Au2Re6-Q colloids, exhibiting disassembly in acidic (pH = 4.5) conditions modeling a lysosomal environment. The counter-ion effect of polyethylenimine causes the release of Re6-Q units from the colloids, while the binding with lysozyme restricts their protonation in acidified conditions. The enhanced luminescence response of Re6-S on the disassembly of Au2Re6-S colloids in the lysosomal environment allows us to determine their high lysosomal localization extent through the colocalization assay, while the low luminescence of Re6-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 Au2 complexes, but the contribution of the apoptotic pathway differentiates the cytotoxic effect of the colloids from that of the Au2 complex arisen from the necrotic processes.
