Image-guided surgery plays a crucial role in realizing complete tumor removal, reducing postoperative recurrence and increasing patient survival. However, imaging of tumor lesion in the typical metabolic organs, e.g., kidney and liver, still has great challenges due to the intrinsic nonspecific 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 postoperative recurrence. The NIR peptide probe first specifically recognizes αvβ3 integrin overexpressed in renal cancer cells, then is cleaved by MMP-2/9, which is up-regulated in the tumor microenvironment. The probe residue spontaneously self-assembles into nanofibers that exhibit an excretion-retarded effect in the kidney, which contributes to a high signal-to-noise (S/N) ratio in orthotopic RCC mice. Intriguingly, the TER effect also enables precisely identifying eye-invisible tiny lesions (<1 mm), which contributes to complete tumor removal and significantly reduces the postoperative recurrence compared with traditional surgery. Finally, the TER strategy is successfully employed in high-performance identification of human RCC in an ex vivo kidney perfusion model. Taken together, this NIR peptide probe based on the TER strategy is a promising method for detecting tumors in metabolic organs in diverse biomedical applications.

Chemotherapy has been validated unavailable for treatment of renal cell carcinoma (RCC) in clinic due to its intrinsic drug resistance. Sensitization of chemo‐drug response plays a crucial role in RCC treatment and increase of patient survival. Herein, a recognition‐reaction‐aggregation (RRA) cascaded strategy is utilized to in situ construct peptide‐based superstructures on the renal cancer cell membrane, enabling specifically perturbing the permeability of cell membranes and enhancing chemo‐drug sensitivity in vitro and in vivo. First, P1‐DBCO can specifically recognize renal cancer cells by targeting carbonic anhydrase IX. Subsequently, P2‐N3 is introduced and efficiently reacts with P1‐DBCO to form a peptide P3, which exhibits enhanced hydrophobicity and simultaneously aggregates into a superstructure. Interestingly, the superstructure retains on the cell membrane and perturbs its integrity/permeability, allowing more doxorubicin (DOX) uptaken by renal cancer cells. Owing to this increased influx, the IC50 is significantly reduced by nearly 3.5‐fold compared with that treated with free DOX. Finally, RRA strategy significantly inhibits the tumor growth of xenografted mice with a 3.2‐fold enhanced inhibition rate compared with that treated with free DOX. In summary, this newly developed RRA strategy will open a new avenue for chemically engineering cell membranes with diverse biomedical applications.

Real-time imaging of the tumour boundary is important during surgery to ensure that sufficient tumour tissue has been removed. However, the current fluorescence probes for bioimaging suffer from poor tumour specificity and narrow application of the imaging window used. Here, we report a bioactivated in vivo assembly (BIVA) nanotechnology, demonstrating a general optical probe with enhanced tumour accumulation and prolonged imaging window. The BIVA probe exhibits active targeting and assembly induced retention effect, which improves selectivity to tumours. The surface specific nanofiber assembly on the tumour surface increases the accumulation of probe at the boundary of the tumor. The blood circulation time of the BIVA probe is prolonged by 110 min compared to idocyanine green. The assembly induced metabolic stability broaden the difference between the tumor and background, obtaining a delayed imaging window between 8–96 h with better signal-to-background contrast (>9 folds). The fabricated BIVA probe permits precise imaging of small sized (<2 mm) orthotopic pancreatic tumors in vivo. The high specificity and sensitivity of the BIVA probe may further benefit the intraoperative imaging in a clinical setting.