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Overcoming the Limits of Hypoxia in Photodynamic Therapy: A Carbonic Anhydrase IX-Targeted Approach

Authors
Jung, Hyo SungHan, JiyouShi, HuKoo, SeyoungSingh, HardevKim, Hyo-JinSessler, Jonathan L.Lee, Jin YongKim, Jong-HoonKim, Jong Seung
Issue Date
7-6월-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://scholar.korea.ac.kr/handle/2021.sw.korea/83151
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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