Multimodal imaging nanoprobes are urgently sought because they can integrate different imaging func- tion into individual nanoplatform and provide more comprehensive and accurate information for the diagnosis of early-stage tumor. Lanthanide-based upconversion nanoparticles （UCNPs） are regarded as promising nanoplatforms to fabricate these probes. Herein, we firstly developed the active core-active shell structured NaYbF4：Tm@NaGdF4：Yb-PVP UCNPs with the average diameter of 13.23 ＋ 0.96 nm as multimodal imaging probes. These water-dispersible nanoprobes presented excellent near-infrared to near-infrared （NIR-to-NIR） upconversion luminescence （UCL） performance, which is favorable for optical bioimaging due to deeper tissue penetration and autofluorescence reduction. After coated with the NaGdF4：Yb active shell, the UCL emission intensity at 800 nm increased by 7.2 times. These nanoprobes exhibited a desirable longitudinal relaxivity （rl = 3.58 L/（mmol s）） and strong X-ray attenuation property （58.84 HU L/g）. The cytotoxicity assessment, histology analysis and biodistribution study revealed that NaYbF4：Tm@NaGdF4：Yb-PVP UCNPs had relatively low cytotoxicity and negligible organ toxicity. These UCNPs were applied for NIR-to-NIR UCL imaging in vivo. More importantly, the detection of small tumor was successfully achieved under Trweighted MRI and CT imaging modalities after intravenous injection of these UCNPs. These results revealed that NaYbF4：Tm@NaGdF4：Yb-PVP UCNPs could serve as promising NIR-to-NIR UCL/MRI/CT trimodal imaging probes.
Tao WangMin YangJiahui HuangYanzhi ZhaoHonglei WangShuang LengJinxing ChenGuoying SunJianhua Liu
