title: The role of photosensitizer molecular charge and structure on the efficacy of photodynamic therapy against Leishmania parasites.
abstract: Photodynamic therapy (PDT) is emerging as a potential therapeutic modality in the clinical management of cutaneous leishmaniasis (CL). In order to establish a rationale for effective PDT of CL, we investigated the impact of the molecular charge and structure of photosensitizers on the parasitic phototoxic response. Two photosensitizers from the benzophenoxazine family that bear an overall cationic charge and two anionic porphyrinoid molecules were evaluated. The photodynamic activity of the photosensitizers decreases in the following order: EtNBSe > EtNBS > BpD > PpIX. The studies suggest that compared to hydrophobic anionic photosensitizers, the hydrophilic cationic benzophenoxazine analogs provide high effectiveness of PDT possibly due to (1) their strong attraction to the negatively charged parasitic membrane, (2) their hydrophilicity, (3) their high singlet oxygen quantum yield, and (4) their efficacy in targeting intracellular organelles.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Oleg E
authors.initials: OE
authors.lastname: Akilov
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kosaka
authors.forename: Katie
authors.initials: K
authors.lastname: O'Riordan
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Song
authors.forename: Margaret
authors.initials: M
authors.lastname: Sherwood
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Flotte
authors.forename: James W
authors.initials: JW
authors.lastname: Foley
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D007891:Leishmania / Q000187:drug effects / Q000648:ultrastructure; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008027:Light; D015394:Molecular Structure; D015388:Organelles / Q000187:drug effects; D010078:Oxazines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D026082:Singlet Oxygen / Q000737:chemistry / Q000378:metabolism; D013045:Species Specificity
chemical_list: D010078:Oxazines; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; C039203:phenoxazine