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고려대학교, 협성대학교

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J. Am. Chem. Soc., 2017, 139 (22), pp 7595-7602 | DOI: 10.1021/jacs.7b02396 Overcoming the Limits of Hypoxia in Photodynamic Therapy: A Carbonic Anhydrase IX-Targeted Approach

Hyo Sung Jung^†#⊥, Jiyou Han^‡§⊥, Hu Shi^∥⊥, Seyoung Koo^†, Hardev Singh^†, Hyo-Jin Kim^‡, Jonathan L. Sessler^*#, Jin Yong Lee^*∥, Jong-Hoon Kim^*‡, and Jong Seung Kim^*†

^†Department of Chemistry and ^‡Department of Biotechnology, Laboratory of Stem Cells and Tissue Regeneration, College of Life Sciences & Biotechnology, Korea University, Seoul 02841, Korea
^§ Department of Biological Sciences, Laboratory of Stem Cell Research and Biotechnology, Hyupsung University, Hwasung-si 18330, Korea
^∥ Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea
^# Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712-1224, United States

Author Contributions
^⊥H.S.J., J.H., and H.S. contributed equally.

^*Corresponding Authors

Abstract

A major challenge in photodynamic cancer therapy (PDT) is avoiding PDT-induced hypoxia, which can lead to cancer recurrence and progression through activation of various angiogenic factors and significantly reduce treatment outcomes. Reported here is an acetazolamide (AZ)-conjugated BODIPY photosensitizer (AZ-BPS) designed to mitigate the effects of PDT-based hypoxia by combining the benefits of anti-angiogenesis therapy with PDT. AZ-BPS showed specific affinity to aggressive cancer cells (MDA-MB-231 cells) that overexpress carbonic anhydrase IX (CAIX). It displayed enhanced photocytotoxicity compared to a reference compound, BPS, which is an analogous PDT agent that lacks an acetazolamide unit. AZ-BPS also displayed an enhanced in vivo efficacy in a xenograft mouse tumor regrowth model relative to BPS, an effect attributed to inhibition of tumor angiogenesis by both PDT-induced ROS generation and CAIX knockdown. AZ-BPS was evaluated successfully in clinical samples collected from breast cancer patients. We thus believe that the combined approach described here represents an attractive therapeutic approach to targeting CAIX-overexpressing tumors.

논문정보

형식Research article
게재일2017년 05월 (BRIC 등록일 2017-05-16)
연구진국내(교신)+국외 연구진
분야 생명과학 > 세포생물학
피인용횟수60회 이상 인용된 논문 (상위피인용논문 등록일 2020-03-13)

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