Abstract

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.

Highlights

  • Real-time imaging of the tumour boundary is important during surgery to ensure that sufficient tumour tissue has been removed

  • We have demonstrated that the enzyme triggered in situ nanofibers assembly exhibited typical aggregation/assembly induced retention (AIR) effect to allow the fluorescent probes to accumulate near the tumor for a long time, extending the imaging time[20]

  • All the results indicated that both hydrophilic mPEG tail and IR783 labeling contributed to the solubility of molecules in aqueous solution

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Summary

Introduction

Real-time imaging of the tumour boundary is important during surgery to ensure that sufficient tumour tissue has been removed. The most famous probe is indocyanine green (ICG), which is a Food and Drug Administration (FDA)–approved near-infrared fluorescent dye, has been used in clinical intraoperative navigation[13]. These small molecules lack of active targeting and showing poor retention in tumor, which narrowed the detection window for complicated surgery[11]. The aggregation-caused quenching (ACQ) effect of such fluorescence dyes limited the molecular accumulation in tumor and the photobleaching behavior confused the imaging Another way in recent years, the delivery of fluorescent probes in vivo has attracted much attention[18].

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