Molecular Engineering of Near-Infrared-II Photosensitizers with Steric-Hindrance Effect for Image-Guided Cancer Photodynamic Therapy |
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Authors: | Shuai Gao Sheng Yu Yongming Zhang Aihua Wu Sihang Zhang Guoguang Wei Hao Wang Zeyu Xiao Wei Lu |
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Affiliation: | 1. Minhang Hospital and School of Pharmacy, State Key Laboratory of Molecular Engineering of Polymers, Key Laboratory of Smart Drug Delivery Ministry of Education, Fudan University, Shanghai, 201199 China;2. Institute of Molecular Medicine, Renji Hospital and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 China;3. National Pharmaceutical Engineering and Research Center, State Institute of Pharmaceutical Industry, Shanghai, 201203 China |
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Abstract: | The design of photosensitizers (PSs) with fluorescence in the second near-infrared (NIR-II, 1000–1700 nm) window remains a challenge, as the introduction of donor or acceptor units with excessively strong electron-withdrawing or donating ability leads to longer-wavelength emission but insufficient production of singlet oxygen (1O2). In this study, a series of acceptor-donor-acceptor-donor-acceptor-type PSs are designed by adjusting the steric hindrance of the molecules. Compound BNET forms a dihedral angle of 88° with a nearly vertically twisted backbone to show that the intensity of local emission in the first near-infrared (750–900 nm) region declines in the aggregated state, while the emission peaks of twisted intramolecular charge transfer span over 1000 nm with significant enhancement. The albumin-bound NIR-II PS nanoparticles exhibit efficient 1O2 generation, good photostability and biocompatibility, and negligible dark toxicity. The nanoparticles demonstrate high specific NIR-II fluorescence imaging of tumor lesions as well as effective image-guided photodynamic therapy in mice bearing orthotopic colon cancer or pancreatic cancer. The designed NIR-II PS nanoparticles show great potential for biomedical applications. |
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Keywords: | near-infrared-II photodynamic therapy photosensitizers steric hindrance twisted intramolecular charge transfer |
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