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Biotin-conjugated Ru(II) complexes with AIE characteristics as mitochondria-targeted photosensitizers for enhancing photodynamic therapy by disrupting cellular redox balance.
- Source :
-
European Journal of Medicinal Chemistry . Jan2024, Vol. 264, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- The potential use of Ru(II) complexes as photosensitizers (PSs) in photodynamic therapy (PDT) has gained significant attention. In comparison with fluorophores with aggregation-caused quenching (ACQ), fluorophores with aggregation-induced emission (AIE) characteristics exhibit sustained fluorescence and dispersibility in aqueous solutions. PSs with AIE characteristics have received much attention in recent years. Herein, we reported two novel biotin-conjugated Ru(II) polypyridyl complexes (Ru1 and Ru2) with AIE characteristics. When exposed to 460 nm (10 mW cm−2) light, Ru1 and Ru2 exhibited outstanding photostability and photocatalytic activity. Ru1 and Ru2 could efficiently generate singlet oxygen and induce pUC19 DNA photolysis when exposed to 460 nm light. Interestingly, both Ru1 and Ru2 also functioned as catalysts for NADH oxidation when exposed to 460 nm light. The presence of biotin fragments in Ru1 and Ru2 enhanced the specific uptake of these complexes by tumor cells. Both complexes showed minimal toxicity to selected cells in the dark. Nevertheless, the phototoxicity of both complexes significantly increased upon 460 nm light irradiation for 15 min. Further experiments revealed that Ru2 primarily accumulated in mitochondria and might bind to mitochondrial DNA. Under 460 nm light irradiation, Ru2 induced the generation of reactive oxygen species (ROS) and NADH depletion disrupting intracellular redox homeostasis in A549 cells, activating the mitochondrial apoptosis pathway resulting in up-regulation of apoptotic marker caspase-3, effectively damaged A549 cell DNA and arrested A549 cell cycle in the S phase. In vivo anti-tumor experiments were conducted to assess the effects of Ru2 on tumor growth in A549 tumor-bearing mice. The results showed that Ru2 effectively inhibited tumor growth under 460 nm light irradiation conditions. These findings indicate that Ru2 has great potential as a targeted photosensitizer for mitochondrial targeting imaging and photodynamic therapy of tumors. [Display omitted] • Two biotin-conjugated Ru(II) complexes with AIE characteristics were synthesized. • Ru1 and Ru2 exhibited outstanding photostability and photocatalytic activity. • Ru2 had potent targeting abilities for A549 cells and mitochondria. • Ru2 could enhance photodynamic therapy by disrupting cellular redox balance. • Ru2 could suppress tumor growth in A549 xenograft-bearing mice under 460 nm light. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 264
- Database :
- Academic Search Index
- Journal :
- European Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 174471706
- Full Text :
- https://doi.org/10.1016/j.ejmech.2023.115985