Bichromophoric BODIPY and Biotin Tagged Terpyridyl Ruthenium(II) Complexes for Cellular Imaging and Photodynamic Therapy

Abstract

A perceived drawback of ruthenium(II) polypyridyl photosensitizers for phototherapeutic applications is their inadequate absorption in the visible region. Ru(II) dyads attached to lightharvesting organic chromophores are studied to address this issue. Biotin-appended compounds having one chromophore, namely BODIPY (boron-dipyrromethene) (1) and Ru(II)-(tpy) 2 (2), or a dyad system containing BODIPY linked to Ru(II)-(tpy) 2 via a diphenylacetylene linker (3) were prepared and studied as photodetection agent and photosensitizes for Photodynamic Therapy (PDT) applications. The bichromophoric 3 with a strong absorption profile (ɛ � 71000 M À 1 cm À 1 at λ max = 503 nm) and high singlet oxygen quantum yield (Φ Δ = 0.63 in DMSO) was studied for PDT activity. This complex produced a superoxide anion radical via type-I and singlet oxygen via type-II photosensitization processes on light exposure, as evidenced from DNA photo-cleavage experiments and in vitro DCFDA assay using reactive oxygen species scavengers/quenchers. Dyad 3 displayed an apoptotic photo-cytotoxic effect against HeLa and H1299 cancer cells with a photocytotoxicity index (PI) value of > 625 in HeLa cells with a PDT efficacy much superior to those of its monochromophoric analogs 1 and 2. The intrinsic emission of complex 3, utilized for cellular imaging, showed selectivity towards lysosomes. Finally, the remarkable potential of complex 3 was evidenced using a clinically relevant 3D multicellular tumor spheroid model.

Mitochondria-targeted ruthenium(ii) complexes for photodynamic therapy and GSH detection in living cells

“…It has been reported that the content of GSH in normal cells is much higher than that of Cys and Hcy, and the content of GSH in some tumor cells increases to about 5 times that of normal cells. 7,8 Therefore,…”

“…30-200 μM), and is at around 1-10 mM in healthy live cells. 7,8 Imbalances in GSH levels are often associated with numerous diseases, including cancer, AIDS, liver damage, skin lesions, Alzheimer's disease, cardiovascular diseases, and edema. [9][10][11][12] The overexpression of GSH in cancer cells highlights the necessity of quantitatively detecting GSH for the early detection and prevention of the disease.…”

“…36,37 Glutathione, one of the most abundant cellular thiols, plays a crucial role in protecting the mitochondrial redox environment to prevent or repair oxidative damage, but an excess of GSH in tumour cells can directly counteract the ROS triggered by the resulting photosensitiser, thus affecting the photodynamic therapy effect. 7,8 Currently, there are numerous reports in the literature on the study of photosensitisers targeting mitochondria for photodynamic therapy. 38–40 For example, Wang's group reported three compounds, RuZ1, RuZ2 and RuZ3, which can target mitochondria and induce apoptosis by increasing the level of reactive oxygen species in SKO3CR cells leading to a decrease in the mitochondrial membrane potential with a higher selectivity and specificity than those of cisplatin.…”

Exploiting Orthogonal C–C Cross-Coupling Reactions for Chemistry-on-the-Complex: Modular Assembly of 2,6-Di(quinolin-8-yl)pyridine Ruthenium(II) Photosensitizer Triads

“…These transformations represent two of the most versatile methodologies that render this method amenable to related fields such as charge accumulation, 14 artificial photosynthesis, 15 singlet O 2 generation, 16,17 hydrogen generation, 18 photodynamic therapy, 19,20 or cellular imaging. 21 ■ RESULTS AND DISCUSSION Introduced in detail above, improved synthetic methods are highly desired to, e.g., easily introduce sensitive donor and acceptor moieties. In the past (Scheme 2a), such reactions required the individual syntheses of two corresponding ligands and the stepwise coordination afterward, which, in turn, limited the accessible set of functionalities due to excessively tedious synthetic efforts.…”

“…We will show the introduction, interconversion, and utilization of the orthogonal functional groups via Suzuki–Miyaura and/or Sonogashira cross-coupling reactions (Scheme b,c). These transformations represent two of the most versatile methodologies that render this method amenable to related fields such as charge accumulation, artificial photosynthesis, singlet O 2 generation, , hydrogen generation, photodynamic therapy, , or cellular imaging …”