An Intramolecular Rotor-Bridged Dimeric Cyanine Photothermal Transducer for Efficient Near-Infrared II Fluorescence Imaging-Guided Mitochondria-Targeted Phototherapy
Abstract
Near-infrared (NIR) heptamethine cyanine (HCy) dyes are promising photothermal transducers for image-guided cancer treatment owing to their prominent photophysical properties and high photothermal conversion ability. However, HCy photothermal transducers usually have poor photostability due to degradation induced by the self-generated reactive oxygen species. Herein, a novel mitochondria-targeting dimeric HCy dye, named dimeric oBHCy, is rationally designed, exhibiting strong near-infrared II (NIR-II) fluorescence emission, high photothermal conversion efficiency (PCE), and excellent photostability. The large π-conjugation and drastic intramolecular motion of the diphenol rotor in the dimeric oBHCy enhance the nonradiative energy dissipation and suppress the intersystem crossing process, thereby achieving a high PCE (49.2%) and improved photostability. Impressively, dimeric oBHCy can precisely target mitochondria and induce mitochondrial damage upon NIR light irradiation. Under the guidance of in vivo NIR-II fluorescence imaging, efficient NIR light-activated photothermal therapy of 4T1 breast tumors is accomplished with a tumor inhibitory rate of 96% following a single injection of the dimeric oBHCy. This work offers an innovative strategy for designing cyanine photothermal transducers with integrated NIR-II fluorescence and photothermal properties for efficient cancer theranostics.
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Dimeric oBHCy has intense NIR-II fluorescence emission, a high photothermal conversion efficiency, and exceptional photostability.
“This distinctive molecular architecture endowed dimeric oBHCy with intense NIR-II fluorescence emission, a high photothermal conversion efficiency (PCE), and exceptional photostability.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [96]
Dimeric oBHCy precisely localizes to cellular mitochondria and efficiently induces mitochondrial damage upon NIR irradiation.
“Dimeric oBHCy demonstrated the capability to precisely localize to cellular mitochondria and efficiently induce mitochondrial damage upon NIR irradiation.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [96]
Li et al. reported a mitochondria-targeted dimeric cyanine dye, dimeric oBHCy, featuring two heptamethine cyanine moieties connected via a bisphenol linker at the central polymethine position.
“Li et al. reported a mitochondria-targeted dimeric cyanine dye (dimeric oBHCy), featuring two heptamethine cyanine moieties connected via a bisphenol linker at the central polymethine position (Fig. 4b)96.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [96]
Cites
Hu, Z., Fang, C., Li, B., Zhang, Z., Cao, C., Cai, M., Su, S., Sun, X., Shi, X., Li, C., et al. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0494-0 · Cited by 1,126 · see citing works
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Design strategies and applications of cyanine dyes in phototherapy
Yuan, J., Yang, H., Huang, W., Liu, S., Zhang, H., Zhang, X., & Peng, X. (2025) · Chemical Society Reviews · doi:10.1039/d3cs00585b · Cited by 143 · see citing works
Organic small-molecule NIR-II fluorophores for tumor phototheranostics
Xiang, D., Wang, Z., Zheng, H., Tang, Y., & Li, Q. (2026) · Light: Science & Applications · doi:10.1038/s41377-026-02212-w · Cited by 22 · see citing works
“4b) 96 .”
- Authors
- Yu, J.-F., Li, J., & Li, M.
- Affiliations
- Central South University (CN)
- Hunan University (CN)
- Corresponding author
- Li, Ming
- ORCID
- Venue
- ACS Sensors
- Publisher
- American Chemical Society (ACS)
- Published
- 2024-07-03
- Volume
- 9
- Issue
- 7
- Pages
- 3581-3593
- ISSN
- 2379-3694 (ISSN-L)
- OpenAlex
- W4400285260
- Cited by
- 16
- References
- 1
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 3
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Sensors (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Science and Technology of Hunan Province (2017XK2027)
- National Natural Science Foundation of China (51871246)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- heptamethine cyanine, NIR-II fluorescence, photothermal therapy, mitochondrial targeting, photostability, non-radiative energy dissipation, breast cancer, 4T1 tumor, theranostics
- MeSH terms
- Photothermal Therapy, Animals, Carbocyanines, Female, Fluorescent Dyes, Humans, Infrared Rays, Mice, Inbred BALB C, Mitochondria, Phototherapy, Dimerization, Cell Line, Tumor, Mice, Optical Imaging
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