A novel NIR-II nanoprobe for precision imaging of micro-meter sized tumor metastases of multi-organs and skin flap

Abstract

A novel small organic molecule nano-NIR-II probe is successfully designed and synthesized. IT-TQT NPs demonstrate unprecedented sensitivity in micro-meter small tumor detection, up to 90 µm. The necrotic area in mouse and porcine skin avulsion injuries can be accurately predicted in advance. These will be of great significance for tumor detection and treatment and avoid secondary surgery for skin avulsion injuries. • Development of a novel nanoprobe based on a new type small-molecular NIR-II dye—IT-TQT. • For the first time, micro-meter sized tumor metastases (up to 90 µm) can be detected by optical imaging, which is ten times improvement comparing to the results reported before. • Early prediction of necrosis in skin avulsion injury in porcine has been successfully achieved by IT-TQT NPs. Near-infrared window II (NIR-II, 1000 – 1700 nm) imaging shows high promise for medical applications. Novel NIR-II dyes are the driving force to realize and broaden the biomedical applications of this newly rising imaging technique. Herein, we designed a novel small molecular NIR-II dye IT-TQT using a new strategy and further loaded the dye into DSPE-PEG 2000 to obtain IT-TQT nanoparticles (NPs) for bioimaging. Specifically, IT-TQT was integrated a novel component 6,7-di(thiophen-2-yl)- [1] , [2] , [5] thiadiazolo[3,4-g] quinoxaline (TQT) as electron acceptor and the indole group widely presented in pharmaceuticals as a novel electron donor. Taking advantage of the excellent photophysical properties of IT-TQT nanoprobe (diameter: 11.2 nm; maximum emission: 1015 nm), IT-TQT NPs clearly delineated tumors in subcutaneous mice models and realized the detection of even micro-meter (down to 90 µm) ultrasmall tumors presented in multiple organs in living tumor metastases mice models. Furthermore, the vasculatures as small as 63.5 µm in diameter were also identified in mice blood vessel imaging using IT-TQT NPs. Lastly, the survival area of the small animal mice and large animal porcine skin flap were successfully visualized by IT-TQT NPs. Overall, IT-TQT nanoprobe has high potential for broad biomedical applications and clinical translation.