An Octopus probe for high-performance >1,300 nm NIR-II fluorescence molecular imaging of cancer

Z Zhennan Peng (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) H Haoran Liu (Marine Biogeochemistry Division, GEOMAR Helmholtz Centre for Ocean Research) H Huaxi Wang (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) R Runying Long (Material Innovation Institute for Life Sciences and Energy, The University of Hong Kong Shenzhen Institute of Research and Innovation) Q Qin Yang (Department of Chemical and Biomolecular Engineering) Z Zigang Lu (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) W Wenjun Xu (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) Z Zhiwei Yin (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) L Liming Zhang F Feiran Zhang (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) X Xiaodong Tian (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) X Xianglin Ji (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) Z Zijian Jiang (Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong) Y Yi Chen H Haonan Lu (Material Innovation Institute for Life Sciences and Energy, The University of Hong Kong Shenzhen Institute of Research and Innovation) H Hongjie Dai (The University of Hong Kong-SIRI , , ,)

Abstract

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.

Article Details

Volume / Issue Vol. 123, Issue 18
Published May 05, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (16)

Z

Zhennan Peng

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

H

Haoran Liu

Marine Biogeochemistry Division, GEOMAR Helmholtz Centre for Ocean Research

H

Huaxi Wang

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

R

Runying Long

Material Innovation Institute for Life Sciences and Energy, The University of Hong Kong Shenzhen Institute of Research and Innovation

Q

Qin Yang

Department of Chemical and Biomolecular Engineering

Z

Zigang Lu

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

W

Wenjun Xu

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

Z

Zhiwei Yin

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

L

Liming Zhang

F

Feiran Zhang

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

X

Xiaodong Tian

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

X

Xianglin Ji

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

Z

Zijian Jiang

Department of Chemistry, Mechanical Engineering and School of Biomedical Sciences, The University of Hong Kong

Y

Yi Chen

H

Haonan Lu

Material Innovation Institute for Life Sciences and Energy, The University of Hong Kong Shenzhen Institute of Research and Innovation

H

Hongjie Dai

The University of Hong Kong-SIRI , , ,