Polymeric micelles of zinc protoporphyrin for tumor targeted delivery based on EPR effect and singlet oxygen generation.
Polymeric micelles of zinc protoporphyrin (ZnPP) with water soluble biocompatible and amphiphilic polymer, polyethylene glycol (PEG) demonstrated unique characteristics to target tumor tissues selectively based on the enhanced permeability and retention (EPR) effect. The micellar macromolecular drug of ZnPP (SMA-ZnPP and PEG-ZnPP) previously showed notable anticancer activity as a consequence of selective tumor targeting ability and its potent HO-1 inhibitory potential, resulting in suppressed biliverdin/bilirubin production in tumors thereby leading to oxystress induced tumor cell killing. Furthermore, recent findings also showed that ZnPP efficiently generated reactive singlet oxygen under illumination of visible light, laser, or xenon light source, which could augment its oxystress induced cell killing abilities. In the present paper, we report the synergistic effects of light induced photosensitizing capabilities and HO-1 inhibitory potentials of these unique micelles when tested in vitro and in vivo on tumor models under localized, mild illumination conditions using a tungsten-xenon light source. The results indicate that these water soluble polymeric micelles of ZnPP portend to be promising candidates for targeted chemotherapy as well as photodynamic therapy against superficial tumors as well as solid tumors located at light penetrable depths.
Iyer
Arun K
AK
Laboratory of Microbiology & Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
Greish
Khaled
K
Seki
Takahiro
T
Okazaki
Shoko
S
Fang
Jun
J
Takeshita
Keizo
K
Maeda
Hiroshi
H
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy*; D010539:Permeability; D010778:Photochemotherapy; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011524:Protoporphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026082:Singlet Oxygen
D004791:Enzyme Inhibitors; D008823:Micelles; D011108:Polymers; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D026082:Singlet Oxygen; D011092:Polyethylene Glycols; D051547:Heme Oxygenase-1