Non-Invasive Optical Guided Tumor Metastasis/Vessel Imaging by Using Lanthanide Nanoprobe with Enhanced Down-Shifting Emission beyond 1500 nm

Visualization of tumor vessels/metastasis and cerebrovascular architecture is vitally important for analyzing pathological states of brain diseases and a tumor's abnormal blood vessels to improve cancer diagnoses. In vivo fluorescence imaging using second near-infrared emission beyond 1500 nm (NIR-IIb) has emerged as a next generation optical imaging method with significant improvement in imaging sensitivity and spatial resolution. Unfortunately, a highly biocompatible probe capable of generating NIR-IIb emission with sufficient brightness and uniformed size is still scarce. Here, we have proposed the poly(acrylic acid) (PAA)-modified NaLnF4:40Gd/20Yb/2Er nanorods (Ln = Y, Yb, Lu, PAA-Ln-NRs) with enhanced downshifting NIR-IIb emission, high quantum yield (QY), relatively narrow bandwidth (∼160 nm), and high biocompatibility via Ce3+ doping for high performance NIR-IIb bioimaging. The downshifting emission beyond 1500 nm is improved by 1.75-2.2 times with simultaneously suppressing the upconversion (UC) path in Y, Yb, and Lu hosts via Ce3+ doping. Moreover, compared with the traditionally used Y-based host, the QY of NIR-IIb emission in the Lu-based probe in water is improved from 2.2% to 3.6%. The explored bright NIR-IIb emitted PAA-Lu-NRs were used for high sensitivity small tumor (∼4 mm)/metastatic tiny tumor detection (∼3 mm), tumor vessel visualization with high spatial resolution (41 μm), and brain vessel imaging. Therefore, our findings open up the opportunity of utilizing the lanthanide based NIR-IIb probe with bright 1525 nm emission for in vivo optical-guided tumor vessel/metastasis and noninvasive brain vascular imaging.