The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50-75%. Advanced real-time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near-infrared (NIR-II) window has the potential to revolutionize the field due to its high spatial resolution, low background signal, and deep tissue penetration properties, but NIR-II dyes with adequate in vivo performance and safety profiles are scarce. A novel NIR-II fluorophore, XW-03-66, with a fluorescence quantum yield (QY) of 6.0% in aqueous media is reported. XW-03-66 self-assembles into nanoparticles (≈80 nm) and has a systemic circulation half-life (t1/2 ) of 11.3 h. In mouse models of human papillomavirus (HPV)+ and HPV- OSCC, XW-03-66 outperformed indocyanine green (ICG), a clinically available NIR dye, and enabled intraoperative NIR-II image-guided resection of the tumor and adjacent draining lymph node with negative margins. In vitro and in vivo toxicity assessments revealed minimal safety concerns for in vivo applications.
Keywords: NIR-II margin delineation; NIR-II probe; intraoperative imaging; mesoscopic solute-rich clusters; organic nanofluorophore; self-assembling.
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