title: Effect of Metalation on Porphyrin-Based Bifunctional Agents in Tumor Imaging and Photodynamic Therapy.
abstract: Herein we report the syntheses and comparative photophysical, electrochemical, in vitro, and in vivo biological efficacy of 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-cyanine dye (HPPH-CD) and the corresponding indium (In), gallium (Ga), and palladium (Pd) conjugates. The insertion of a heavy metal in the HPPH moiety makes a significant difference in FRET (Förster resonance energy transfer) and electrochemical properties, which correlates with singlet oxygen production [a key cytotoxic agent for photodynamic therapy (PDT)] and long-term in vivo PDT efficacy. Among the metalated analogs, the In(III) HPPH-CD showed the best cancer imaging and PDT efficacy. Interestingly, in contrast to free base HPPH-CD, which requires a significantly higher therapeutic dose (2.5 μmol/kg) than imaging dose (0.3 μmol/kg), the corresponding In(III) HPPH-CD showed excellent imaging and therapeutic potential at a remarkably low dose (0.3 μmol/kg) in BALB/c mice bearing Colon26 tumors. A comparative study of metalated and corresponding nonmetalated conjugates further confirmed that STAT-3 dimerization can be used as a biomarker for determining the level of photoreaction and tumor response.
authors.forename: Nayan J
authors.initials: NJ
authors.lastname: Patel
authors.forename: Yihui
authors.initials: Y
authors.lastname: Chen
authors.forename: Penny
authors.initials: P
authors.lastname: Joshi
authors.forename: Paula
authors.initials: P
authors.lastname: Pera
authors.forename: Heinz
authors.initials: H
authors.lastname: Baumann
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Missert
authors.affiliation: Department of Material and Life Science, Graduate School of Engineering, Osaka University, ALCA and SENTAN, Japan Science and Technology Agency (JST) , 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.|Department of Chemistry and Nano Science, Ewha Womans University , Seoul, 120-750, Korea.
authors.forename: Kei
authors.initials: K
authors.lastname: Ohkubo
authors.affiliation: Department of Material and Life Science, Graduate School of Engineering, Osaka University, ALCA and SENTAN, Japan Science and Technology Agency (JST) , 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.|Department of Chemistry and Nano Science, Ewha Womans University , Seoul, 120-750, Korea.|Faculty of Science and Engineering, Meijo University, ALCA and SENTAN, Japan Science and Technology Agency (JST) , Nagoya, Aichi 468-0073, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Fukuzumi
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health , Frederick, Maryland 21702, United States.
authors.forename: Roger R
authors.initials: RR
authors.lastname: Nani
authors.affiliation: Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health , Frederick, Maryland 21702, United States.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schnermann
authors.affiliation: Department of Chemistry, University of Houston , 112 Fleming Bldg, Houston, Texas 77204, United States.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Houston , 112 Fleming Bldg, Houston, Texas 77204, United States.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, University of Houston , 112 Fleming Bldg, Houston, Texas 77204, United States.
authors.forename: Karl M
authors.initials: KM
authors.lastname: Kadish
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Pandey
mesh_terms: D000818:Animals; D031541:Fluorescence Resonance Energy Transfer; D008670:Metals / Q000737:chemistry*; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology*; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D008670:Metals; D011166:Porphyrins