Tumor microenvironment enhanced NIR II fluorescence imaging for tumor precise surgery navigation via tetrasulfide mesoporous silica-coated Nd-based rare-earth nanocrystals

In vivo fluorescent imaging by using the new contrast agents emitted at short-wavelength infrared region (NIR II, 1000-1700 nm) presents an unprecedent advantages in imaging sensitivity and spatial resolution over traditional near-infrared (NIR) light. Recently, Nd-based rare-earth nanocrystals have attracted considerable attention due to the high quantum yield (similar to 40%) of their emission at NIR II. However, undesirable capture by reticuloendothelial system to bring strong background signal is unsatisfying for tumor discrimination. Here, GSH-sensitive tetrasulfide bond incorporated mesoporous silica shell has entrusted onto Nd-based down-conversion nanocrystals (DCNPs) surface to totally quench the fluorescence of DCNPs. After RGD conjugation on the silica surface, the NIR II contrast agents could actively target to liver tumors. Then tetrasulfide bonds can be broken during the silica framework decomposing in cytoplasm under high GSH concentration to result in NIR II fluorescence explosive recover. Benefiting from this specific response under tumor microenvironment, the NIR II signal in other organs was markedly reduced, while the signal-to-background ratio is prominently enhanced in tumors. Then, solid liver tumors were successfully resected under the guidance of our GSH responsive NIR II fluorescent imaging with no recurrence after 20-day of surgery. Meanwhile, by combining with the ignorable side effects, the Nd-based nanoprobes vastly improved the imaging resolution of tumor margin, opening a paradigm of NIR II fluorescent imaging-guided surgery.