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