Self-assembled NIR-II Fluorophores with Ultralong Blood Circulation for Cancer Imaging and Image-guided Surgery.

Abstract

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-PEGnk (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-PEG2k can self-assemble into vesicular micelles and exhibited minimal immunogenicity, low binding affinities, ultralong blood circulation (t1/2 = 59.5 h), and a supercontrast ratio in vivo. Most importantly, L6-PEG2k 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-PEG2K as self-assembling molecular probes with long-circulation persistence for routine preoperative tumor assessment and precise intraoperative image-guided resection.

• Authors: Yang Li, Jianfeng Gao, Shuping Wang, Mingxia Du, Xiaowen Hou, Tian Tian, Xue Qiao, Zhiquan Tian, Peter J Stang, Shijun Li, Xuechuan Hong, Yuling Xiao
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 65 Issue 3 Pg. 2078-2090 (02 10 2022) ISSN: 1520-4804 [Electronic] United States
• PMID: 34949094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Contrast Media
• Fluorescent Dyes
• Polyethylene Glycols

Topics

• Animals
• Brain Neoplasms (diagnostic imaging, therapy)
• Cell Line, Tumor
• Contrast Media (chemical synthesis, chemistry, pharmacokinetics)
• Drug Design
• Fluorescent Dyes (chemical synthesis, chemistry, pharmacokinetics)
• Glioma (diagnostic imaging, therapy)
• Half-Life
• Humans
• Mice
• Mice, Inbred BALB C
• Polyethylene Glycols (chemistry)
• Quantum Theory
• Spectroscopy, Near-Infrared (methods)
• Surgery, Computer-Assisted
• Tissue Distribution
• Transplantation, Heterologous