期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 65, 期 3, 页码 2078-2090出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c01615
关键词
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资金
- National Key R&D Program of China [2020YFA0908800]
- NSFC [81773674, 81573383, 21763002, 82111530209, 91959103]
- Shenzhen Science and Technology Research Grant [JCYJ20190808152019182]
- Hubei Province Scientific and Technical Innovation Key Project [2020BAB058]
- Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology [2019020701011429]
- Local Development Funds of Science and Technology Department of Tibet [XZ202102YD0033C, XZ202001YD0028C]
- Natural Science Foundation of Hubei [2019CFB679]
- Health Commission of Hubei Province Scientific Research Project [WJ2021Q031]
- Fundamental Research Funds for the Central Universities
This study presents a new generation NIR-II probe, L6-PEG(2k), with exceptional fluorescence performance and long circulation time, enabling tumor targeting and accumulation in vivo, providing image guidance for precise surgery.
Complete excision of the last remaining 1-2% of tumor tissue without collateral damage remains particularly challenging. Herein, we report thiophenthiadiazole (TTD)-derived fluorophores L6-PEG(nk) (n = 1, 2, 5) as new-generation NIR-II (1000-1700 nm) probes with exceptional nonfouling performance and significantly high fluorescence quantum yields in water. L6-PEG(2k) can self-assemble into vesicular micelles and exhibited minimal immunogenicity, low binding affinities, ultralong blood circulation (t(1/2) = 59.5 h), and a supercontrast ratio in vivo. Most importantly, L6-PEG(2k) achieved excellent in vivo CT-26 and U87MG tumor targeting and accumulation (>20 d) through intraperitoneal or intravenous injection. A subcutaneous U87MG tumor and orthotopic brain glioma were successfully resected under NIR-II FIGS in our animal model via intraperitoneal injection in an extended time window 48 144 h). This study highlights the potential of using L6-PEG(2K) as self-assembling molecular probes with long-circulation persistence for routine preoperative tumor assessment and precise intraoperative image-guided resection.
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