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, Jong Seung Kim

Research output: Contribution to journalArticle

114 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7595-7602
Number of pages8
JournalJournal of the American Chemical Society
Volume139
Issue number22
DOIs
Publication statusPublished - 2017 Jun 7

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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