Home » Key Drug Discovery Articles » A novel class of ruthenium-based photosensitizers effectively kills in vitro cancer cells and in vivo tumors

A novel class of ruthenium-based photosensitizers effectively kills in vitro cancer cells and in vivo tumors

Fong J1, Kasimova K2, Arenas Y1, Kaspler P1, Lazic S1, Mandel A1, Lilge L2,3. Photochem Photobiol Sci. 2015 Feb 10.

1Theralase Technologies, 1945 Queen St. East, Toronto, ON M4L 1H7, Canada.

2Princess Margaret Cancer Centre/University Health Network, 101 College Street 15-310, Toronto, Canada.
3University of Toronto, Department of Medical Biophysics, 610 University Ave., Toronto, Canada.


The photo-physical and photo-biological properties of two small (<2 kDa),  novel  Ru(ii) photosensitizers (PSs) referred to as TLD1411 and TLD1433 are presented. Both PSs are highly water-soluble, provide only very limited luminescence emission at 580-680 nm following excitation at 530 nm, and demonstrate high photostability with less than 50% photobleaching at radiant exposures H = 275 J cm-2 (530 nm irradiation). It was previously shown that these two photosensitizers exhibit a large singlet oxygen (1O2) quantum yield (Φ (Δ) ∼0.99 in acetonitrile). Their photon-mediated efficacy to cause cell death (λ = 530 nm, H = 45 J cm-2) was tested in vitro in colon and glioma cancer cell lines (CT26.WT, CT26.CL25, F98, and U87) and demonstrated a strong photodynamic effect with complete cell death at concentrations as low as 4 and 1 μM for TLD1411 and TLD1433, respectively. Notably, dark toxicity was negligible at concentrations less than 25 and 10 μM for TLD1411 and TLD1433, respectively. The ability of the photosensitizers to initiate Type I photoreactions was tested by exposing photosensitizers-treated U87 cells to light under hypoxic conditions (pO2 < 0.5%), which resulted in a complete loss of the PDT effect. In vivo, the maximum tolerated doses 50 (MTD50) were determined to be 36 mg kg-1 (TLD1411) and 103 mg kg-1 (TLD1433) using the BALB/c murine model. In vivo growth delay studies in the subcutaneous colon adenocarcinoma CT26.WT murine model were conducted at a photosensitizer dose equal to 0.5 and 0.2 MTD50 for TLD1411 and TLD1433, respectively. 4 hours post PS injection, tumours were irradiated with continuous wave or pulsed light sources (λ = 525-530 nm, H = 192 J cm-2). Overall, treatment with continuous wave light demonstrated a higher tumour destruction efficacy when compared to pulsed light. TLD1433 mediated PDT resulted in statistically significant longer animal survival compared to TLD1411. Two-thirds of TLD1433-treated mice survived more than 100 days (p < 0.01) whereas TLD1411-treated mice did not survive longer than 20 days. Here we present evidence that two novel photosensitizers have very potent photo-biological properties and are able to cause PDT-mediated cell death in both in vitro cell culture models and in vivo tumour regression.

Go To Photochemical & Photobiological Sciences


Figure Legend: Accumulation of 1 mM TLD1433 in SCC4 cell (red) predominantly outside the nucleous (DAPI stain, blue) after 4 hrs. (Curtesy Dr. Angelika Rueck)

ruthenium-based photosensitizers effectively kills in vitro cancer cells and in vivo tumors. Global Medical Discovery










Figure Legend: 3D structure of TLD1433 with the green central Ruthenium (II) surrounded by Nitrogen (blue) and the ligand side chains with Sulphur (yellow). Carbon atoms are grey and Hydrogen white.

ruthenium-based photosensitizers. Global Medical Discovery