Construction of lanthanide-doped upconversion nanoparticle-Uelx Europaeus Agglutinin-I bioconjugates with brightness red emission for ultrasensitive in vivo imaging of colorectal tumor

Abstract

Lanthanide-doped upconversion nanoparticles (UCNPs)-based active targeting optical bioimaging has attracted tremendous scientific interest because of its noninvasive real-time signal feedback, superior tissue penetration depth and high spatial resolution in early diagnosis of disease. Herein, we synthesize a novel carboxy-terminated silica coated NaErF4: 10% Yb@NaYF4: 40% Yb@NaNdF4: 10% Yb@NaGdF4: 20% Yb UCNPs (termed as UCNP@SiO2-COOH) with 808 nm near-infrared (NIR) excitation and bright 655 nm upconversion luminescence (UCL) emission for realizing deep tissue imaging. Under 808 nm NIR laser excitation (1.5 W cm−2), the UCL of UCNP@SiO2-COOH with relative low concentration (2 mg mL−1) can be successfully visualized under a chicken breast slice with 10 mm thickness. After conjugated with various molecules including NH2-PEG3400-COOH, peptide D-SP5 and Uelx Europaeus Agglutinin-I (UEA-I), biodistributions, clearance pathways and tumor-targeting capacities of the UCNP@SiO2-COOH and corresponding bioconjugates (termed as UCNP@SiO2-PEG, UCNP@SiO2-D-SP5 and UCNP@SiO2-UEA-I, respectively) were investigated by tracking the UCL intensities of livers, kidneys and tumors. Both of in vitro and in vivo experimental results reveal that there is no significant difference for their in vivo biodistributions and clearance pathways. The UCNP@SiO2-UEA-I exhibits much higher SW480 tumor-targeting capacity than those of other bioconjugates. In particular, the as-prepared UCNP@SiO2-UEA-I even to visualize ultrasmall (c.a. 3 mm3 in volume) subcutaneous SW480 tumor in Balb/c nude mouse through intravenous administration. The study implies that the red UCL emitted UCNPs with a minimized heating effect is suitable for deep tissue biomedical imaging and UCNP@SiO2-UEA-I can serve as an efficient optical probe for early diagnosis of SW480 tumor.