AUTHOR=Pewklang Thitima , Chansaenpak Kantapat , Bakar Siti Nursyahirah , Lai Rung-Yi , Kue Chin Siang , Kamkaew Anyanee 

TITLE=Aza-BODIPY based carbonic anhydrase IX: Strategy to overcome hypoxia limitation in photodynamic therapy

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.1015883

DOI=10.3389/fchem.2022.1015883

ISSN=2296-2646

ABSTRACT=<p>Hypoxia caused by photodynamic therapy (PDT) is a major hurdle to cancer treatment since it can promote recurrence and progression by activating angiogenic factors, lowering therapeutic efficacy dramatically. In this work, AZB-I-CAIX<sub>2</sub> was developed as a carbonic anhydrase IX (CAIX)-targeting NIR photosensitizer that can overcome the challenge by utilizing a combination of CAIX knockdown and PDT. AZB-I-CAIX<sub>2</sub> showed a specific affinity to CAIX-expressed cancer cells and enhanced photocytotoxicity compared to AZB-I-control (the molecule without acetazolamide). Moreover, selective detection and effective cell cytotoxicity of AZB-I-CAIX<sub>2</sub> by PDT in hypoxic CAIX-expressed murine cancer cells were achieved. Essentially, AZB-I-CAIX<sub>2</sub> could minimize tumor size in the tumor-bearing mice compared to that in the control groups. The results suggested that AZB-I-CAIX<sub>2</sub> can improve therapeutic efficiency by preventing PDT-induced hypoxia through CAIX inhibition.</p>