Overcoming the Limits of Hypoxia in Photodynamic Therapy: A Carbonic Anhydrase IX-Targeted Approach
- Authors
- Jung, HS[Jung, Hyo Sung]; Han, J[Han, Jiyou]; Shi, H[Shi, Hu]; Koo, S[Koo, Seyoung]; Singh, H[Singh, Hardev]; Kim, HJ[Kim, Hyo-Jin]; Sessler, JL[Sessler, Jonathan L.]; Lee, JY[Lee, Jin Yong]; Kim, JH[Kim, Jong-Hoon]; Kim, JS[Kim, Jong Seung]
- Issue Date
- 7-Jun-2017
- Publisher
- AMER CHEMICAL SOC
- Citation
- JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.139, no.22, pp.7595 - 7602
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
- Volume
- 139
- Number
- 22
- Start Page
- 7595
- End Page
- 7602
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/28593
- DOI
- 10.1021/jacs.7b02396
- ISSN
- 0002-7863
- 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.
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- Appears in
Collections - Science > Department of Chemistry > 1. Journal Articles
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