An Indocyanine Green-Based\nNanocluster for Imaging\nOrthodox Endometriosis Lesions with Negative Contrast

Indocyanine green (ICG), as the sole near-infrared dye\nFDA-approved,\nis limited in biomedical applications because of its poor photostability,\nlack of targeting, and rapid removal in vivo. Herein, we presented\na nanoformulation of poly-l-lysine–indocyanine green–hyaluronic\nacid (PIH) and demonstrated that it can image orthodox endometriosis\n(EM) lesions with a negative contrast. The PIH nanocluster, with an\naverage diameter of approximately 200 nm, exhibited improved fluorescence\nphotostability and antioxidant ability compared to free ICG. In the\nin vivo imaging, EM lesions were visualized, featuring apparent voids\nand clear boundaries. After colocalizing with the green fluorescent\nprotein, we concluded that the contrast provided by PIH peaked at\n4 h postinjection and was observable for at least 8 h. The negative\ncontrast, clear boundaries, and enhanced observable time might be\ndue to the low permeation of PIH to lesions and the enhanced retention\non the surfaces of lesions. Thus, our findings suggest an ICG-based\nnanoprobe with the potential to diagnose abdominal diseases.