A Novel Histochemical Staining Approach for Rare‐Earth‐Based Nanoprobes

Abstract Rare‐earth (RE)‐based nanoparticles have exhibited broad potential applications in the biomedical field owing to their unique magnetic and optical properties. But until now, there has been no reliable histochemical staining method developed for probing the distribution of RE‐based nanoparticles in different organs and tissues, which is imperative for evaluating the targeting ability and safety profiles of RE‐based nanoparticles used as the diagnostic probe and the therapeutic agent. Herein, the authors propose a novel and effective staining approach for identifying RE‐based nanoprobes in tissues through unique chromogenic reactions between Chlorophosphonazo III and RE 3+ , which is independent of the element type. More importantly, a staining color analysis method based on the specific RGB range‐selective integration of the stained images is developed for establishing a quantitative relationship between the optical density and RE 3+ concentration in the tissue slices.