Image-guided surgery plays a crucial role in realizing complete tumor-removal, reducing postoperative recurrence and increasing of patient survival. However, imaging of tumor lesion in the typical metabolic organs, e. g., kidney and liver, still remain great challenges due to the intrinsic non-specific accumulation of imaging probes in those organs. Herein, we report an in situ self-assembled Near Infrared (NIR)-peptide probe with tumor-specific excretion retarded (TER) effect in tumor lesions, enabling high performance imaging of human renal cell carcinoma (RCC) and achieving complete tumor-removal, ultimately reducing the postoperative recurrence. The NIR-peptide probe firstly specifically recognizes αvβ3 integrin overexpressed in renal cancer cells, then is cleaved by MMP-2/9 that up-regulated in tumor microenvironment. The probe residue spontaneously self-assembles into nanofibers that exhibit an excretion retarded effect in kidney, which contributes to a high signal-to-noise (S/N) ratio in orthotopic RCC mice. Intriguingly, TER effect also enables to precisely identify eye-invisible tiny lesions (< 1 mm) which contributes to complete tumor-removal and significantly reduce the postoperative recurrence compared with traditional surgery. Finally, TER strategy successfully employs in high performance identification of human RCC in ex vivo kidney perfusion model. Taken together, this NIR-peptide probe based on TER strategy is a promising method for detecting tumors in metabolic organs in diverse biomedical applications.
ACS nano. 2020 Jan 13 [Epub ahead of print]
Hong-Wei An, Dayong Hou, Rui Zheng, Man-Di Wang, Xiang-Zhong Zeng, Wu-Yi Xiao, Tong-Da Yan, Jia-Qi Wang, Chang-Hao Zhao, Li-Ming Cheng, Jin-Ming Zhang, Lu Wang, Zi-Qi Wang, Hao Wang, Wanhai Xu