| Title: | Comparison of low-molecular-weight ligand and whole antibody in prostate-specific membrane antigen targeted near-infrared photoimmunotherapy |
| Authors: | Nakajima, Kohei Browse this author →KAKEN DB |
| Miyazaki, Fuka Browse this author |
| Terada, Kazuki Browse this author |
| Takakura, Hideo Browse this author |
| Suzuki, Motofumi Browse this author →KAKEN DB |
| Ogawa, Mikako Browse this author →KAKEN DB |
| Keywords: | Low-molecular-weight ligand |
| Molecular targeted therapy |
| Near-infrared photoimmunotherapy (NIR-PIT) |
| Photodynamic therapy (PDT) |
| Photosensitizer |
| Issue Date: | 20-Nov-2021 |
| Publisher: | Elsevier |
| Journal Title: | International journal of pharmaceutics |
| Volume: | 609 |
| Start Page: | 121135 |
| Publisher DOI: | 10.1016/j.ijpharm.2021.121135 |
| Abstract: | Near-infrared photoimmunotherapy (NIR-PIT) is a cancer phototherapy that uses antibody-IR700 conjugate (AbIR700) and NIR light. Ab-IR700 forms aggregates on the plasma membranes of targeted cancer cells after light exposure, inducing lethal physical damage within the membrane. Low-molecular-weight (LMW) ligands are candidate targeting moieties instead of antibodies, but whether LMW-IR700 conjugates induce cell death by aggregation, the same mechanism as Ab-IR700, is unknown. Thus, we investigated differences in cytotoxicity and mechanisms between LMW-IR700 and Ab-IR700 targeting prostate-specific membrane antigen (PSMA). Both conjugates decreased cell viability to the same degree after light irradiation, but different morphological changes were observed in PSMA-positive LNCaP cells by microscopy. Cell swelling and bleb formation were induced by Ab-IR700, but only swelling was observed in cells treated with LMW-IR700, suggesting the cells were damaged via different cytotoxic mechanisms. However, LMW-IR700 induced bleb formation, a hallmark of NIR-PIT with Ab-IR700, when singlet oxygen was quenched or LMW-IR700 was localized only on the plasma membrane. Moreover, the water-soluble axial ligands of LMW-IR700 were cleaved, consistent with previous reports on AbIR700. Thus, the main cytotoxic mechanisms of Ab-IR700 and LMW-IR700 differ, although LMW-IR700 on the plasma membrane can cause aggregation-mediated cytotoxicity as well as Ab-IR700. |
| Rights: | © 2021, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/87680 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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