Photosensitizer-conjugated tryptophan-containing peptide ligands as new dual-targeted theranostics for cancers.
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.
Molecular Imaging & Therapy Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea.
Jisu
J
Kim
Department of Chemistry & Nanoscience, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.
Jihyun
J
Chae
Department of Chemistry & Nanoscience, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.
Jun Soo
JS
Kim
Precision Medicine Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea.
Sung-Ho
SH
Goh
Molecular Imaging & Therapy Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea; Precision Medicine Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea. Electronic address: ydchoi@ncc.re.kr.
Yongdoo
Y
Choi
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D032389:Myocytes, Smooth Muscle; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000068936:Theranostic Nanomedicine; D014364:Tryptophan / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
C572557:GE11 peptide; D008024:Ligands; D010455:Peptides; D017319:Photosensitizing Agents; D014364:Tryptophan; D066246:ErbB Receptors
Activatable; EGFR target; Fluorescence imaging; Photodynamic therapy; Theranostics