Photoimmunotherapy of hepatocellular carcinoma-targeting Glypican-3 combined with nanosized albumin-bound paclitaxel

Author:

Hanaoka Hirofumi1,Nakajima Takahito1,Sato Kazuhide1,Watanabe Rira1,Phung Yen2,Gao Wei2,Harada Toshiko1,Kim Insook3,Paik Chang H4,Choyke Peter L1,Ho Mitchell2,Kobayashi Hisataka1

Affiliation:

1. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Building 10, Room B3B69, MSC1088, Bethesda, MD 20892, USA

2. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA

3. Applied/Developmental Research Directorate, Leidos Biomedical Research Inc, Frederick National Laboratory, Frederick, MD 21702, USA

4. Nuclear Medicine Department, Warren Grant Magnuson Clinical Center, Radiology & Imaging Science, Warren Grant Magnuson Clinical Center, NIH, Bethesda, MD 20892, USA

Abstract

Aim: Effectiveness of Glypican-3 (GPC3)-targeted photoimmunotherapy (PIT) combined with the nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for hepatocellular carcinoma was evaluated. Materials & methods: GPC3 expressing A431/G1 cells were incubated with a phthalocyanine-derivative, IRDye700DX (IR700), conjugated to an anti-GPC3 antibody, IR700-YP7 and exposed to near-infrared light. Therapeutic experiments combining GPC3-targeted PIT with nab-paclitaxel were performed in A431/G1 tumor-bearing mice. Results: IR700-YP7 bound to A431/G1 cells and induced rapid target-specific necrotic cell death by near-infrared light exposure in vitro. IR700-YP7 accumulated in A431/G1 tumors. Tumor growth was inhibited by PIT compared with nontreated control. Additionally, PIT dramatically increased nab-paclitaxel delivery and enhanced the therapeutic effect. Conclusion: PIT targeting GPC3 combined with nab-paclitaxel is a promising method for treating hepatocellular carcinoma.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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