Comparison of low-molecular-weight ligand and whole antibody in prostate-specific membrane antigen targeted near-infrared photoimmunotherapy.

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a cancer phototherapy that uses antibody-IR700 conjugate (Ab-IR700) 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 Ab-IR700. 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.

• Authors: Kohei Nakajima, Fuka Miyazaki, Kazuki Terada, Hideo Takakura, Motofumi Suzuki, Mikako Ogawa
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 609 Pg. 121135 (Nov 20 2021) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 34571072 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Antigens, Surface
• Ligands
• Photosensitizing Agents
• FOLH1 protein, human
• Glutamate Carboxypeptidase II

Topics

• Antigens, Surface
• Cell Line, Tumor
• Glutamate Carboxypeptidase II
• Humans
• Immunotherapy
• Infrared Rays
• Ligands
• Male
• Molecular Targeted Therapy
• Photosensitizing Agents
• Phototherapy
• Prostatic Neoplasms (therapy)
• Xenograft Model Antitumor Assays