Intraoperative Surgical Margin Assessment by NIR-II Imaging with Urine Excretable Nd-Based Nanoprobe in Breast Cancers

Lanthanide neodymium (Nd)-based nanocrystals exhibit exceptional near-infrared II (NIR-II) fluorescence imaging properties, like narrow and multi-peak emissions, long luminescence lifetime, and good photostability. However, long-term accumulation in the reticuloendothelial system restrains their clinical applications due to toxicity in vivo. Here, a biodegradable hollow virus-like neodymium oxide (Nd2O3) Nd-nanoprobe is presented that is modified with cyclic arginine-glycine-aspartic acid (cRGD) pentapeptide, showing remarkable cancer-targeting ability and NIR-II fluorescence imaging features. The nanoprobe is biodegraded to 4-6 nm Nd2O3 nanogranules in vivo, and the pharmacokinetics of the nanoprobe demonstrated its rapid urine excretion and negligible systematic toxicity. Moreover, this nanoprobe can accurately identify malignant lesions from normal tissues in xenograft and transgenic mice models and precisely navigate breast cancer surgery under NIR-II imaging guidance. Taken together, this Nd2O3-based nanoprobe enables real-time, dynamic delineation and accurate resection of cancers guided by NIR-II fluorescence imaging with great potential for future clinical translation during breast-conservative surgery. Long-term accumulation in the reticuloendothelial system restrains clinical applications of Lanthanide neodymium-based nanocrystals. Here, a biodegradable hollow virus-like neodymium oxide nanoprobe is presented and modified with cyclic arginineglycine-aspartic acid pentapeptide, showing rapid urine excretion, negligible systematic toxicity, remarkable cancer-targeting ability, and the second near-infrared fluorescence imaging features. Generally, these nanocrystals enable great potential for future clinical translation during breast-conservative surgery.image