Water-soluble polymer conjugates of ZnPP for photodynamic tumor therapy.
Zn-protoporphyrin (ZnPP) is a promising candidate for cancer therapy. It is known to inhibit heme-oxygenase-1 (HO-1), resulting in suppressed biliverdin/bilirubin production accompanying lowered antioxidative capacity. As a consequence, a significant suppression of tumor growth in vivo was reported. Recent findings also showed that ZnPP efficiently generated reactive singlet oxygen under illumination of visible light. In the present report, we describe the photosensitizing capabilities of water-soluble polymer conjugates of ZnPP as novel compounds for photodynamic therapy against solid tumors. The polymer conjugation made ZnPP water-soluble, thus possible for injection for its aqueous solution. The cellular uptake and photobiological activity of ZnPP derivatives have been tested using a human T-cell leukemia cell line in vitro and demonstrated most potent phototoxic effects of SMA-ZnPP followed by PEG-ZnPP under aerobic conditions.
Regehly
M
M
Institut für Physik, Photobiophysik, Humboldt Universität zu Berlin, Newtonstr. 15, D-12489 Berlin, Germany.
Greish
K
K
Rancan
F
F
Maeda
H
H
Böhm
F
F
Röder
B
B
D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D016503:Drug Delivery Systems; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000528:radiation effects; D010778:Photochemotherapy; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D012995:Solubility; D014867:Water / Q000737:chemistry*
D011108:Polymers; D011524:Protoporphyrins; D014867:Water; C017803:zinc protoporphyrin; D011092:Polyethylene Glycols; D051547:Heme Oxygenase-1; D053148:Caspase 3; D053179:Caspase 7