Aggregation‐Mediated Photoacoustic/NIR‐II and Photodynamic Properties of pH‐Reversible Thiopyrylium Agents: A Computational and Experimental Approach
Abstract
Aggregation profoundly influences the photophysical properties of molecules. Here, a new series of thiopyrylium‐based hemicyanine near‐infrared II (NIR‐II) fluorophores is developed by meticulously adjusting their aggregation states. Notably, the star molecule HTPA exhibits a remarkable pH‐responsive behavior and a significant increase in photoacoustic (PA) intensity when aggregated. Additionally, their behavior and pH reversibility during aggregation formation are systematically investigated, including computational optimization, femtosecond transient absorption spectroscopy, NMR analysis, and single crystal analysis. Finally, an innovative “off ” nanoparticle specifically is designed for effective tumor‐targeted PA/NIR‐II dual‐modal imaging and photodynamic therapy by utilizing a pH‐responsive polymer. The signal‐to‐background ratio (SBR) of PA signals significantly increased to 169 in the region of interest (ROI) in the mouse model when irradiated at 1064 nm. These findings not only provide a promising avenue for future studies of NIR‐II small molecules but also pave the way for significant advances in the field of integrated cancer diagnosis and therapy.
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HTPA NPs specifically targeted mitochondria in tumor cells and effectively suppressed tumor growth through PDT.
“Furthermore, HTPA NPs specifically targeted mitochondria in tumor cells and effectively suppressed tumor growth through PDT.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [239]
The photosensitizing properties of HTPA exhibited pH-dependent behavior, enabling reversible modulation in response to pH variations.
“Notably, the photosensitizing properties of HTPA exhibited pH-dependent behavior, enabling reversible modulation in response to pH variations.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [239]
In 4T1 tumor-bearing mouse models, HTPA NPs demonstrated significant accumulation at the tumor site, with fluorescence signals peaking at 96 h post injection.
“In 4T1 tumor-bearing mouse models, HTPA NPs demonstrated significant accumulation at the tumor site, with fluorescence signals peaking at 96 h post injection.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [239]
In aqueous environments, the aggregation process of HTPA, driven by twisted intramolecular charge transfer and strong π-π stacking interactions, enhanced non-radiative transitions.
“In aqueous environments, the aggregation process of HTPA, driven by twisted intramolecular charge transfer (TICT) and strong π-π stacking interactions, enhanced non-radiative transitions.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [239]
The aggregation of HTPA amplified the PA signal and retained the NIR-II imaging capability.
“This not only amplified the PA signal but also retained the NIR-II imaging capability.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [239]
Under 1064 nm laser irradiation, HTPA NPs enabled high-contrast PA imaging, achieving an SNR of 96.
“Under 1064 nm laser irradiation, HTPA NPs enabled high-contrast PA imaging, achieving an SNR of 96.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [239]
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- Authors
- Liu, Y., Zhang, Z., Hou, X., Ding, Q., Zeng, S., Shen, H., Gong, W., Ding, T., Mahmood, Z., Zeng, X., Ren, B., Hu, W., Hong, X., Ding, D., & Xiao, Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- Korea University (KR)
- Research Center for Biomedical Optics and Molecular Imaging Key Laboratory of Biomedical Imaging Science and System Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China
- Hong Kong University of Science and Technology (HK)
- Wuhan University (CN)
- Guangdong University of Technology (CN)
- Northwestern Polytechnical University (CN)
- Nankai University (CN)
- Corresponding author
- Xiao, Yuling
- ORCID
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2025-02-03
- Volume
- 37
- Issue
- 10
- Pages
- e2420006-e2420006
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- OpenAlex
- W4407081826
- Cited by
- 30
- References
- 23
- Citations by year
- 2026: 14 · 2025: 16
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Update notices
- correction (2025-05-30)
- Open access
- closed
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Key Research and Development Program of China (2023YFC3605502)
- National Natural Science Foundation of China (22477129, 82273796, 82372005, 82171986)
- Taishan Scholar Project of Shandong Province (TSQN202306320)
- Natural Science Foundation of Shandong Province (ZR2023MB085)
- Basic and Applied Basic Research Foundation of Guangdong Province (2023A1515012649)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Keywords
- hemicyanine, NIR-II fluorophores, photoacoustic imaging, photodynamic therapy, aggregation, dual-modality imaging, tumor-targeted nanoparticles, pH-responsive polymers, cancer diagnosis and treatment
- MeSH terms
- Animals, Carbocyanines, Fluorescent Dyes, Humans, Hydrogen-Ion Concentration, Infrared Rays, Photochemotherapy, Photosensitizing Agents, Mice, Nanoparticles, Photoacoustic Techniques
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