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- 2017년 07월호
[J Am Chem Soc.] Overcoming the Limits of Hypoxia in Photodynamic Therapy: A Carbonic Anhydrase IX-Targeted Approach.고려대, 성균관대, 텍사스대/정호성, 김종성*, 김종훈*, 이진영*, Jonathan L. Sessler*
- 출처
- J Am Chem Soc.
- 등재일
- 2017 Jun 7
- 저널이슈번호
- 139(22):7595-7602. doi: 10.1021/jacs.7b02396. Epub 2017 May 10.
- 내용
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.
Author information
Jung HS1, Han J2, Shi H3, Koo S, Singh H, Kim HJ, Sessler JL1, Lee JY3, Kim JH, Kim JS.
1Department of Chemistry, The University of Texas at Austin , Austin, Texas 78712-1224, United States.2Department of Biological Sciences, Laboratory of Stem Cell Research and Biotechnology, Hyupsung University , Hwasung-si 18330, Korea.3Department of Chemistry, Sungkyunkwan University , Suwon 440-746, Korea.
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편집위원
종양 치료에 있어서 hypoxia 유발을 피하면서 (anti-angiogenesis) photodynamic therapy (PDT)가 가능한 acetazolamide-BODIPY (AZ-BPS)을 개발한 연구 결과로, carbonic anhydrase IX(CAIX) 억제 및 종양 표적 가능성을 in vitro 및 in vivo 데이터를 제시하며 보여주었다.
덧글달기닫기2017-07-06 15:39:52
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