Bright Aggregation-Induced Emission Dots For Dynamic Tracking And Grading Of Patient-Derived Xenografts In Zebrafish

Cancer prognosis will benefit from a scoring system that could grade malignant traits of patient-derived cells by assessing their growth and metastasis in a living system. Specific tracking of patient-derived cells requires labeling by contrast agents with good signal-to-noise ratio and no specific stain of host tissues. Towards this aim, aggregation-induced emission (AIE) dots are developed for in vivo cancer tracking with emphasis on reproducible optimized formulation and specific fluorescent labeling of cells that enable enhanced spatial temporal resolution in vivo. The importance of energy-dependent AIE dots uptake for patient-derived cell labeling is emphasized to reveal their specific uptake by viable cancer cells. Using optically transparent zebrafish embryo, the ability is demonstrated to follow the engraftment of transplanted AIE dot labeled cells in zebrafish brains over one week. Cells detected outside the brain after 7 d are quantified as metastatic cells. Results from seven clinical samples demonstrate the utility of this methodology to differentiate low engraftment level of benign neoplasms from higher engraftment level and metastasis detected in malignant ovarian cancer specimens. Achieving clinically validated results supports the use of AIE dot labeled patient derived cells in zebrafish xenografts for future cancer prognosis.