An Emerging Molecular Design Approach to Heavy-Atom-Free Photosensitizers for Enhanced Photodynamic Therapy under Hypoxia

Van Nghia Nguyen, Sujie Qi, Sangin Kim, Nahyun Kwon, Gyoungmi Kim, Yubin Yim, Sungnam Park, Juyoung Yoon

Research output: Contribution to journalArticlepeer-review

218 Scopus citations


A novel strategy for designing highly efficient and activatable photosensitizers that can effectively generate reactive oxygen species (ROS) under both normoxia and hypoxia is proposed. Replacing both oxygen atoms in conventional naphthalimides (RNI-O) with sulfur atoms led to dramatic changes in the photophysical properties. The remarkable fluorescence quenching (φPL ≈ 0) of the resulting thionaphthalimides (RNI-S) suggested that the intersystem crossing from the singlet excited state to the reactive triplet state was enhanced by the sulfur substitution. Surprisingly, the singlet oxygen quantum yield of RNI-S gradually increased with increasing electron-donating ability of the 4-R substituents (MANI-S, φΔ ≈ 1.00, in air-saturated acetonitrile). Theoretical studies revealed that small singlet-triplet energy gaps and large spin-orbit coupling could be responsible for the efficient population of the triplet state of RNI-S. In particular, the ROS generation ability of MANI-S was suppressed under physiological conditions due to their self-assembly and was significantly recovered in cancer cells. More importantly, cellular experiments showed that MANI-S still produced a considerable amount of ROS even under severely hypoxic conditions (1% O2) through a type-I mechanism.

Original languageEnglish
Pages (from-to)16243-16248
Number of pages6
JournalJournal of the American Chemical Society
Issue number41
StatePublished - 16 Oct 2019

Bibliographical note

Funding Information:
This study was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP) (No. 2012R1A3A2048814 for J. Y. and No. 2016R1A2B4011522 for S.P.). Mass spectral data were obtained from the Korea Basic Science Institute (Daegu) on a Jeol JMS 700 high-resolution mass spectrometer.

Publisher Copyright:
Copyright © 2019 American Chemical Society.


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