*Article* **Novel Fluorescent Probe Based on Rare-Earth Doped Upconversion Nanomaterials and Its Applications in Early Cancer Detection**

**Zhou Ding 1, Yue He 1, Hongtao Rao 1, Le Zhang 1, William Nguyen 2, Jingjing Wang 1, Ying Wu 1, Caiqin Han 1, Christina Xing 2, Changchun Yan 1, Wei Chen 2,3,\* and Ying Liu 1,\***


**Abstract:** In this paper, a novel rare-earth-doped upconverted nanomaterial NaYF4:Yb,Tm fluorescent probe is reported, which can detect cancer-related specific miRNAs in low abundance. The detection is based on an upconversion of nanomaterials NaYF4:Yb,Tm, with emissions at 345, 362, 450, 477, 646, and 802 nm, upon excitation at 980 nm. The optimal Yb3+:Tm3+ doping ratio is 40:1, in which the NaYF4:Yb,Tm nanomaterials have the strongest fluorescence. The NaYF4:Yb, Tm nanoparticles were coated with carboxylation or carboxylated protein, in order to improve their water solubility and biocompatibility. The two commonly expressed proteins, miRNA-155 and miRNA-150, were detected by the designed fluorescent probe. The results showed that the probes can distinguish miRNA-155 well from partial and complete base mismatch miRNA-155, and can effectively distinguish miRNA-155 and miRNA-150. The preliminary results indicate that these upconverted nanomaterials have good potential for protein detection in disease diagnosis, including early cancer detection.

**Keywords:** upconversion nanomaterials; novel fluorescent probe; miRNA-155; miRNA-150
