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Self‐Assembly of Mitochondria‐Targeted Photosensitizer to Increase Photostability and Photodynamic Therapeutic Efficacy in Hypoxia
Author(s) -
Jana Batakrishna,
Thomas Ajesh P.,
Kim Sangpil,
Lee In Seong,
Choi Huyeon,
Jin Seongeon,
Park Soo Ah,
Min Seung Kyu,
Kim Chaekyu,
Ryu JaHyoung
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001366
Subject(s) - photosensitizer , photodynamic therapy , mitochondrion , chemistry , reactive oxygen species , biophysics , indocyanine green , apoptosis , cancer research , photochemistry , biochemistry , biology , medicine , pathology , organic chemistry
Abstract 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.