Bioinspired Long-Wavelength Excitable Near-Infrared AIEdots for Endometriosis Targeting and Image-Guided Surgery

Endometriosis（EM）is a non-cancerous and intractable disease in clinic due to the ambiguity of its etiology and mechanism. Surgical removal of the lesions is more efficient method for EM treatment compared with pharmacological intervention. Intraoperative identification of the endometrial ectopic sites is a prerequisite, however, available probes with high specificity remain limited, owing to lack of specific biomarkers. Here, based on a polypeptide derived from VAR2CSA protein (CSA) and a near-infrared AIE material (TPA-TBZ-2), we prepared a CSA AIEdots capable of labeling the EM lesions by a one-step nanoprecipitation method. The nanodots have an absorbance maximum at 610 nm with a wide emission range from 650 to 850 nm and an absolute quantum yield of up to 34% in the aggregation states. Through in vitro assay, the dots could specifically label endometrioid cells (Ishikawa cells), and flow cytometry experiments showed its specific spectral absorption peak, compared with empty particles and scrambled peptide groups. Next, to verify the ability of the dots to label the ectopic endometrium in vivo, we established a mouse model of endometriosis. After injection the dots into model mouse intravenously for 24 hours, the AIE signaling could be specifically detected at the ectopic lesions in an IVIS small animal imaging system. The CSA AIEdots were further used for image-guided EM resection in vivo and showed a high EM-to-normal tissue signal ratio. Taken together, our AIE nanodots-based EM diagnosis system is a promising candidate for EM development monitoring and surgical navigations.