An objective was to explore the photodynamic activity of two cationic
photosensitizers (PS) (benzo[a]phenothiazinium
chloride and benzo[a]phenoselenazinium
chloride) against Mycobacterium bovis BCG both in vitro and in a murine model of BCG-
granuloma. The hypothesis being tested in this study was that cationic molecules could best interact with the negatively charged membrane of BCG as a model for mycobacterial
infection. Cells in culture were incubated with various concentrations of PS and subsequently illuminated using a 635 nm
diode laser. Dark- and light-induced killing profiles were generated as a function of fluence and
dye concentration. In vivo, local injection of the PS into subcutaneous Mycobacterium-induced
granuloma sites in murine model was followed by red light illumination of the same area. A special microscope was fabricated for real-time in vivo fluorescent microscopy to monitor
EtNBS delivery to subcutaneous murine granulomata. Both PS demonstrated good in vitro antimycobacterial photodynamic activity with varying degrees of toxicity under dark conditions. Real time in vivo monitoring of
benzophenothiazine chloride in the mouse model indicated that this fluorescent
photosensitizer was delivered rapidly to the subcutaneous
granuloma site. In vivo,
photosensitizer specific dark- and photo-toxicities depended on the structure, concentration of the
photosensitizer and the light dose utilized. Cationic
phenothiazine photosensitizers are promising candidates for use in anti-mycobacterial
PDT for localized diseases such as cutaneous and pulmonary granulomata.