Overcoming the Limits of Hypoxia in Photodynamic Therapy: A Carbonic Anhydrase IX-Targeted Approach
journal contributionposted on 01.05.2017, 00:00 by 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
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.
Read the peer-reviewed publication
anti-angiogenesis therapyPDT agentcancer recurrenceAZ-BPSBODIPYacetazolamide unitcancer cellsvivo efficacyapproachCAIX knockdownxenograft mouse tumor regrowth modelPDT-induced ROS generationPDT-induced hypoxiaCAIX-overexpressing tumorsbreast cancer patientsBPSreference compoundPhotodynamic TherapyPDT-based hypoxiaCarbonic Anhydrase IX-Targeted Approachoverexpress carbonic anhydrasephotodynamic cancer therapytreatment outcomesAZtumor angiogenesisMDA-MB -231 cellsangiogenic factors