ROS-producing nanomaterial engineered from Cu(I) complexes with P2N2-ligands for cancer cells treating

Bulat A Faizullin; Irina R Dayanova; Alexey V Kurenkov; Aidar T Gubaidullin; Alina F Saifina; Irek R Nizameev; Kirill V Kholin; Mikhail N Khrizanforov; Aisylu R Sirazieva; Igor A Litvinov; Alexandra D Voloshina; Anna P Lyubina; Guzel V Sibgatullina; Dmitry V Samigullin; Elvira I Musina; Igor D Strelnik; Andrey A Karasik; Asiya R Mustafina

doi:10.1186/s11671-023-03912-7

ROS-producing nanomaterial engineered from Cu(I) complexes with P₂N₂-ligands for cancer cells treating

Discov Nano. 2023 Oct 30;18(1):133. doi: 10.1186/s11671-023-03912-7.

Authors

Bulat A Faizullin¹, Irina R Dayanova², Alexey V Kurenkov², Aidar T Gubaidullin², Alina F Saifina², Irek R Nizameev³, Kirill V Kholin⁴, Mikhail N Khrizanforov^{2

5}, Aisylu R Sirazieva², Igor A Litvinov², Alexandra D Voloshina², Anna P Lyubina², Guzel V Sibgatullina⁶, Dmitry V Samigullin^{6

7}, Elvira I Musina², Igor D Strelnik^{2

5}, Andrey A Karasik², Asiya R Mustafina²

Affiliations

¹ Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Str., Kazan, Russia, 420088. bulat_fayzullin95@mail.ru.
² Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov Str., Kazan, Russia, 420088.
³ Department of Physics, Kazan National Research Technological University, 68 Karl Marx Str., Kazan, Russia, 420015.
⁴ Department of Nanotechnology in Electronics, Kazan National Research Technical University Named After A.N. Tupolev-KAI, 10 K. Marx Street, Kazan, Russia, 420111.
⁵ Aleksander Butlerov Institute of Chemistry, Kazan Federal University, 1/29 Lobachevski Str., Kazan, Russia, 420008.
⁶ Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevski Str., Kazan, Russia, 420111.
⁷ Institute for Radio-Electronics and Telecommunications, Kazan National Research Technical University Named After A.N. Tupolev-KAI, 10 K. Marx Street, Kazan, Russia, 420111.

Abstract

The work presents core-shell nanoparticles (NPs) built from the novel Cu(I) complexes with cyclic P₂N₂-ligands (1,5-diaza-3,7-diphosphacyclooctanes) that can visualize their entry into cancer and normal cells using a luminescent signal and treat cells by self-enhancing generation of reactive oxygen species (ROS). Variation of P- and N-substituents in the series of P₂N₂-ligands allows structure optimization of the Cu(I) complexes for the formation of the luminescent NPs with high chemical stability. The non-covalent modification of the NPs with triblock copolymer F-127 provides their high colloidal stability, followed by efficient cell internalization of the NPs visualized by their blue (⁓450 nm) luminescence. The cytotoxic effects of the NPs toward the normal and some of cancer cells are significantly lower than those of the corresponding molecular complexes, which correlates with the chemical stability of the NPs in the solutions. The ability of the NPs to self-enhanced and H₂O₂-induced ROS generation is demonstrated in solutions and intracellular space by means of the standard electron spin resonance (ESR) and fluorescence techniques correspondingly. The anticancer specificity of the NPs toward HuTu 80 cancer cells and the apoptotic cell death pathway correlate with the intracellular level of ROS, which agrees well with the self-enhancing ROS generation of the NPs. The enhanced level of ROS revealed in HuTu 80 cells incubated with the NPs can be associated with the significant level of their mitochondrial localization.

Keywords: Chemodynamic therapy; Copper(i) complex; Hydrophilic nanoparticles; Luminescence; ROS generation.

Abstract

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