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Rui-Qin Yang,1– 3 Min Chen,3,4 Qiang Zhang,5 Yi-Yang Gao,1– 3 Kang-Liang Lou,1– 3 Tong-Tong Lin,5 Wen-He Huang,1,2 Yun-Zhu Zeng,6 Yong-Qu Zhang,1– 3 Yong-Ying Dang,1– 3 Lei Ren,5,* Guo-Jun Zhang1,2,4,* 1Cancer Center & Department of Breast and Thyroid Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Key Laboratory for Endocrine-Related Cancer Precision Medicine of Xiamen, Xiang’an Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 3Clinical Central Research Core, Xiang’an Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 5State Key Lab of Physical Chemistry of Solid Surface, College of Materials, Xiamen University, Xiamen, Fujian, People’s Republic of China; 6The Pathology department, Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Jun Zhang, Tel +86-592-2889988, Fax +86-592-2889202, Email gjzhang@xah.xmu.edu.cnPurpose: Tumor-free surgical margin is crucial but challenging in breast-conserving surgery (BCS). Fluorescence imaging is a promising strategy for surgical navigation that can reliably assist the surgeon with visualization Of the tumor in real-time. Notably, finding an optimized fluorescent probe has been a challenging research topic. Herein, we developed a novel near-infrared (NIR) fluorescent probe based on tailored Hepatitis B Core virus-like protein (HBc VLP) and presented the preclinical imaging-guided surgery.Methods: The RGD-HBc160 VLP was synthesized by genetic engineering followed encapsulation of ICG via disassembly-reassembly. The applicability of the probe was tested for cell and tissue binding capacities through cell-based plate assays, x