A bioactivated in vivo assembly (BIVA) nanotechnology fabricated NIR probe for small pancreatic tumor intraoperative navigation imaging

Abstract Visual intraoperative navigation depends on the optical technique for real-time imaging of the boundary of tumor. However, the fluorescence probes now enable for bioimaging are usually lack of tumor specificity and poor imaging window, which limited the further clinical applications. Here, we report a bioactivated in vivo assembly (BIVA) nanotechnology, which provides a universal optical probe delivery system to enhance the targeting specificity, region accumulation and continuous imaging window of the probe. Based on the coupling of BIVA domain and probe, BIVA probe exhibits a synergy mechanism of active targeting and assembly induced retention, which improved the targeting efficiency. In addition, the tumor surface specific nanofiber assembly significantly increases the accumulation of the probe at tumor boundary. The PEGylation of the BIVA probe extended the blood circulation time for 110 min, and the area under the curve (AUC 0-120 h) of tumor was significantly increased by 3.6 times compared with the active targeting probe. As the dynamic assembly difference between tumor and background further enlarges the metabolic difference, we obtained a delayed imaging window between 8-96 hours with better signal-to-background ratio (SBR > 9 times). Our BIVA probe can be used for imaging of small-size (d < 2 mm) orthotopic pancreatic tumors in vivo. The high specificity and sensitivity of the BIVA probe will further benefit the intraoperative navigation imaging in clinical.