Peptide-enhanced tumor accumulation of upconversion nanoparticles for sensitive upconversion luminescence/magnetic resonance dual-mode bioimaging of colorectal tumors.

Currently, it is still a great challenge to develop tumor targeting nanoparticles with high sensitivity and high resolution for improving the non-invasive detection ability of colorectal cancer (CRC) at an early stage. In this study, NaErF4:Yb@NaGdF4:Yb core@shell upconversion nanoparticles (UCNPs) were prepared with high upconversion luminescence (UCL) emission in red light region through adjusting the doping ratios of Er and Yb elements in the core. For biomedical applications, the carboxyl-terminated silica shell was introduced to transfer the as-prepared UCNPs from the organic phase to the aqueous phase, and allowed conjugation with peptide ligands derived from the l-SP5 peptide (i.e., l-SP5-H and l-SP5-C), respectively. Due to the tumor-targeting affinity of the PSP motif in the peptide ligands, the as-prepared peptide functionalized UCNPs (UCNP@SiO2-l-SP5-H and UCNP@SiO2-l-SP5-C) can be used as an active tumor targeting contrast agents for UCL/T1-weighted magnetic resonance (MR) dual-mode imaging. Both the in vitro and in vivo experimental results demonstrated that UCNP@SiO2-l-SP5-C has relatively high affinity for the HCT116 CRC subtype. Moreover, UCNP@SiO2-l-SP5-C can visualize ultra-small subcutaneous xenografted HCT116 tumors (c.a. 13 mm3 in volume) by in vivo UCL imaging. STATEMENT OF SIGNIFICANCE: 1. High red emission UCNPs were synthesized for tumor-targeting dual-mode bioimaging. 2. With tumor-binding affinity peptide, UCNP@SiO2-l-SP5-C shows high HCT116 tumor targeting ability. 3. UCNP@SiO2-l-SP5-C successfully achieves sensitive detection of ultrasmall HCT116 tumors.