Photophysical, electrochemical characteristics and cross-linking of STAT-3 protein by an efficient bifunctional agent for fluorescence image-guided photodynamic therapy

Abstract

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.