title: An investigation into the potential of phenothiazinium-based photo-sensitisers to act as PDT agents.
abstract: 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 (3.15Jcm(-2) over 30min). "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 (ΦΔPhBP) and lipophilicity (logP) of these PhBPs.
  
  
  RESULTS
  "Comet assay" showed EMT-6 incubation with PhBPs under light conditions to produce DNA "tails", which were circa 35μm 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 (ΦΔPhBP>0.7), suggesting the general use of type II mechanisms for photo-sensitization, and were generally lipophilic (logP>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 photo-dynamic anti-tumour activity of the PhBPs tested with the exception of DMMB, which may potentially also target tumour cell membranes.
authors.affiliation: Department of Forensic and Investigative Science, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: F
authors.initials: F
authors.lastname: Harris
authors.affiliation: Department of Forensic and Investigative Science, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Sayed
authors.affiliation: Department of Forensic and Investigative Science, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: S
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Faculty of Science, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Phoenix