An emerging molecular design approach to heavy-atom-free photosensitizers for enhanced photodynamic therapy under hypoxia
Abstract
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 (Φ PL ≈ 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, Φ Δ ≈ 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% O 2 ) through a type-I mechanism.
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“This is because a rigid external environment may effectively inhibit the non-radiative relaxation at its triplet excited state [14], and the environment’s oxygen barrier efficiency/ability may also inhibit the triplet-triplet energy transfer process between the phosphors and the triplet oxygen to reduce the non-radiat…”
Background
- Authors
- Nguyen, V.-N., Qi, S., Kim, S., Kwon, N., Kim, G., Yim, Y., Park, S., & Yoon, J.
- Affiliations
- Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Republic of Korea
- Ewha Womans University (KR)
- Korea University (KR)
- Corresponding author
- Park, Sungnam
- Yoon, Juyoung
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-10-02
- Volume
- 141
- Issue
- 41
- Pages
- 16243-16248
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2978749031
- Cited by
- 457
- References
- 39
- Citations by year
- 2026: 48 · 2025: 65 · 2024: 94 · 2023: 67 · 2022: 68 · 2021: 64 · 2020: 51
- FWCI
- 33.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (2012R1A3A2048814, 2016R1A2B4011522)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- photosensitizers, naphthalimide, sulfur substitution, photodynamic therapy, hypoxia, reactive oxygen species, singlet oxygen quantum yield, intersystem crossing, spin-orbit coupling, fluorescence quenching, self-assembly, cancer cells
- MeSH terms
- Antineoplastic Agents, Cell Survival, HeLa Cells, Humans, Oxygen, Photochemotherapy, Drug Design, Molecular Structure, Photosensitizing Agents
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