Self‐Assembly of Mitochondria‐Targeted Photosensitizer to Increase Photostability and Photodynamic Therapeutic Efficacy in Hypoxia
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- Self‐Assembly of Mitochondria‐Targeted Photosensitizer to Increase Photostability and Photodynamic Therapeutic Efficacy in Hypoxia
- Jana, Batakrishna; Thomas, Ajesh P.; Kim, Sangpil; Lee, In Seong; Choi, Huyeon; Jin, Seongeon; Park, Soo Ah; Min, Seung Kyu; Kim, Chaekyu; Ryu, Ja-Hyoung
- Issue Date
- John Wiley & Sons Ltd.
- CHEMISTRY-A EUROPEAN JOURNAL, v.26, no.47, pp.10695 - 10701
- The development of photosensitizers for cancer photodynamic therapy has been challenging due to their low photostability and therapeutic inefficacy in hypoxic tumor microenvironments. To overcome these issues, we have developed a mitochondria-targeted photosensitizer consisting of an indocyanine moiety with triphenylphosphonium arms, which can self-assemble into spherical micelles directed to mitochondria. Self-assembly of the photosensitizer resulted in a higher photostability by preventing free rotation of the indoline ring of the indocyanine moiety. The mitochondria targeting capability of the photosensitizer allowed it to utilize intramitochondrial oxygen. We found that the mitochondria-targeted photosensitizer localized to mitochondria and induced apoptosis of cancer cells both normoxic and hypoxic conditions through generation of ROS. The micellar self-assemblies of the photosensitizer were further confirmed to selectively localize to tumor tissues in a xenograft tumor mouse model through passive targeting and showed efficient tumor growth inhibition.
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