Photophysical, electrochemical characteristics and cross-linking of STAT-3 protein by an efficient bifunctional agent for fluorescence image-guided photodynamic therapy.
The photophysical, electrochemical and spectroscopic characteristics of a conjugate of 3-devinyl-3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) and a cyanine dye have been investigated both as a linked conjugate and as individual components. A photoexcitation of the HPPH moiety of the conjugate results in electron transfer from the singlet excited state of HPPH (1HPPH*) to the cyanine dye as well as that from the cyanine dye to 1HPPH* and is followed in both cases by facile back electron transfer to the ground state as indicated by time-resolved fluorescence and transient absorption measurements. Intersystem crossing to the triplet excited state (3HPPH*) competes with the electron transfer and 3HPPH* is quenched by oxygen to produce singlet oxygen (1O2), leading to specific covalent cross-linking of the nonactivated signal transducer and activator of transcription (STAT-3). In contrast to excitation of the HPPH moiety, photoexcitation of the cyanine dye unit results in a strong emission at 875 nm, which can be used for efficient tumor imaging. Compared to HPPH alone, the presence of the cyanine dye moiety in the conjugate produces a significantly higher uptake in tumors than in skin. Thus, the HPPH-cyanine dye conjugate can be used as a dual tumor imaging and photodynamic therapy agent.
Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Yihui
Y
Chen
Kei
K
Ohkubo
Min
M
Zhang
E
E
Wenbo
Weiguo
W
Liu
Suresh K
SK
Pandey
Michael
M
Ciesielski
Heinz
H
Baumann
Tracy
T
Erin
Shunichi
S
Fukuzumi
Karl M
KM
Kadish
Robert
R
Fenstermaker
Allan
A
Oseroff
Ravindra K
RK
Pandey
D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000494:pharmacology; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004563:Electrochemistry; D005453:Fluorescence; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D010084:Oxidation-Reduction; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry
D002232:Carbocyanines; D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D026082:Singlet Oxygen