An Octopus probe for high-performance >1,300 nm NIR-II fluorescence molecular imaging of cancer.
In surgical oncology, precise intraoperative delineation of malignant tumors for complete yet non-excessive resection has been challenging. Near-infrared II (NIR-II, 1,000 to 3,000 nm) imaging enables deep-tissue, high-contrast visualization, but clinical translation is limited by the lack of robust probes. Cytalux, the first clinically approved NIR-I (700 to 1,000 nm) probe for folate receptor (FR)-positive cancers, is limited in shallow imaging depth and low tumor to normal tissue contrast. Here, we present "Octopus" (OCTP), a modular multi-arm PEG-based NIR-II probe targeting FR capable of rapid and sustained tumor accumulation upon systemic administration to afford superior tumor-to-background ratios and precise margin visualization by NIR-II imaging, significantly outperforming Cytalux in mouse models. Importantly, we uncovered that NIR-II imaging in the >1,300 nm emission range under NIR-I excitation completely suppressed tissue autofluorescence, allowing unambiguous molecular imaging of residual cancerous cells at tumor margins for resection. Pharmacokinetic and toxicity studies demonstrate rapid clearance, minimal off-target accumulation, and excellent biocompatibility. OCTP enables accurate, background-free >1,300 nm fluorescence-guided tumor surgery, promising as the next-generation NIR-II molecular imaging of cancer.
Authors
Peng Peng, Liu Liu, Wang Wang, Long Long, Yang Yang, Lu Lu, Xu Xu, Yin Yin, Zhang Zhang, Zhang Zhang, Tian Tian, Ji Ji, Jiang Jiang, Chen Chen, Lu Lu, Dai Dai
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