HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >

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

This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Files in This Item:
210404_PSMA-PIT_ver6_1_revised_ver3_combined.pdf6.57 MBPDFView/Open
Please use this identifier to cite or link to this item:

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)
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
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 中島 孝平

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University