title: Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy.
abstract: The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.
authors.affiliation: Xi'an Jiaotong University, School of Life Science and Technology, Institute of Biomedical Analytical Technology and Instrumentation, Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an 710049, ChinabUniversity of Lübeck, I.
authors.forename: Sijia
authors.initials: S
authors.lastname: Wang
authors.affiliation: University of Lübeck, Institute of Biomedical Optics, Peter-Monnik-Weg 4, Lübeck 23562, Germany.
authors.forename: Gereon
authors.initials: G
authors.lastname: Hüttmann
authors.affiliation: University of Lübeck, Institute of Biomedical Optics, Peter-Monnik-Weg 4, Lübeck 23562, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Rudnitzki
authors.affiliation: University of Lübeck, Institute of Biomedical Optics, Peter-Monnik-Weg 4, Lübeck 23562, Germany.
authors.forename: Heyke
authors.initials: H
authors.lastname: Diddens-Tschoeke
authors.affiliation: Xi'an Jiaotong University, School of Life Science and Technology, Institute of Biomedical Analytical Technology and Instrumentation, Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an 710049, China.
authors.forename: Zhenxi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: University of Lübeck, Institute of Biomedical Optics, Peter-Monnik-Weg 4, Lübeck 23562, Germany.
authors.forename: Ramtin
authors.initials: R
authors.lastname: Rahmanzadeh
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry*; D019394:Ki-67 Antigen / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D010778:Photochemotherapy / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D007208:Indocyanine Green