Imidazole metalloporphyrins as photosensitizers for photodynamic therapy: role of molecular charge, central metal and hydroxyl radical production.
The in vitro photodynamic therapy activity of four imidazole-substituted metalloporphyrins has been studied using human (HeLa) and mouse (CT26) cancer cell lines: an anionic Zn porphyrin and a homologous series of three cationic Zn, Pd or InCl porphyrins. A dramatic difference in phototoxicity was found: Pd cationic>InCl cationic>Zn cationic>Zn anionic. HeLa cells were more susceptible than CT26 cells. Induction of apoptosis was demonstrated using a fluorescent caspase assay. The anionic Zn porphyrin localized in lysosomes while the cationic Zn porphyrin localized in lysosomes and mitochondria, as assessed by fluorescence microscopy. Studies using fluorescent probes suggested that the cationic Pd porphyrin produced more hydroxyl radicals as the reactive oxygen species. Thus, the cationic Pd porphyrin has high potential as a photosensitizer and gives insights into characteristics for improved molecular designs.
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
Pawel
P
Mroz
Jayeeta
J
Bhaumik
Dilek K
DK
Dogutan
Zarmeneh
Z
Aly
Zahra
Z
Kamal
Laiqua
L
Khalid
Hooi Ling
HL
Kee
David F
DF
Bocian
Dewey
D
Holten
Jonathan S
JS
Lindsey
Michael R
MR
Hamblin
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D007093:Imidazoles / Q000627:therapeutic use*; D008247:Lysosomes / Q000378:metabolism; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D010778:Photochemotherapy / Q000379:methods*
D007093:Imidazoles; D008665:Metalloporphyrins; C017802:zinc hematoporphyrin; D017665:Hydroxyl Radical