An investigation into the potential of phenothiazinium-based photo-sensitisers to act as PDT agents

Background: There is an urgent need for effective cancer treatments and increasingly, photo-dynamic therapy (PDT) is being used to fulfil this need as it offers a number of advantages over traditional cancer treatments. Here, the potential of a series of phenothiazinium-based photo-sensitisers (PhBPs) as PDT agents is tested. Methods: PhBPs were incubated with EMT-6 tumour cells and erythrocytes respectively under dark and light conditions (3.15J cm(-2) over 30 min). "Comet assay" and haemolytic assay were then used to assess cellular photo-damage induced by these PhBPs. Additionally, in vitro assays were used to determine light adsorption characteristics, singlet oxygen yields (Phi(Delta PhBP)) and lipophilicity (log P) of these PhBPs. Results: "Comet assay" showed EMT-6 incubation with PhBPs under light conditions to produce DNA "tails", which were circa 35 mu m long, indicating the presence of DNA photo-damage. Corresponding incubations under dark conditions led to no such damage. The majority of the PhBPs tested possessed significant singlet oxygen yields (Phi(Delta PhBP) > 0.7), suggesting the general use of type II mechanisms for photosensitization, and were generally lipophilic (log P > 0). Incubation of erythrocytes with these PhBPs in the dark produced between 6% and 19% haemolysis. These levels were generally unaffected by illumination except in the case of DMMB, which showed haemolytic levels increasing from 11% to 61%. Conclusions: It is suggested that DNA may be the primary target for the photodynamic anti-tumour activity of the PhBPs tested with the exception of DMMB, which may potentially also target tumour cell membranes. (C) 2004 Elsevier B.V. All rights reserved.