Photosensitizer-conjugated tryptophan-containing peptide ligands as new dual-targeted theranostics for cancers

Publication date: 20 November 2016 Source:International Journal of Pharmaceutics, Volume 513, Issues 1–2 Author(s): Jisu Kim, Jihyun Chae, Jun Soo Kim, Sung-Ho Goh, Yongdoo Choi Here we report that new dual-targeted theranostic anti-cancer agents can be produced by simple conjugation of photosensitizers with tryptophan-containing peptide ligands via cyclic disulfide linkages. In the proof-of-concept study, photosensitizers conjugated with EGFR-targeting peptide GE11 (C-EGFR) were in close proximity with tryptophan residues in the conjugate, resulting in quenching of its fluorescence and singlet oxygen generation. C-EGFR specifically binds to target receptors on the cancer cell surface, after which it is internalized via receptor-mediated endocytosis. Intracellular cleavage of cyclic disulfide bonds allows separation of the photosensitizers from the tryptophan residue, after which they emit near-infrared (NIR) fluorescence and produce a phototoxic effect in the target cells. This strategy enabled us to accomplish simultaneous real-time NIR fluorescence imaging of EGFR-overexpressing cancer cells with high contrast and selective photodynamic therapy Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research