In Vivo Toxicity of Upconversion Nanoparticles. Overview. Part I

This review synthesizes current research on the in vivo dark toxicity of upconversion nanoparticles (UCNPs) for biomedical applications, including luminescent imaging, diagnostics, and photoinduced therapy. The aim is to assess key toxicity determinants – nanoparticle type, surface coating, concentration, and dose relative to body weight – and to establish safe exposure thresholds. Analysis of comprehensive histological and biochemical studies indicates that UCNPs generally exhibit low toxicity under tested conditions. The most non-toxic concentration identified across studies is 2 mg/mL. For mice, the maximum permissible dose for short-term exposure (12 h) is 10 mg/kg, and for long-term exposure (120 days) is 50 mg/kg. For rats, a dose of 5 mg/kg is safe for both short- and long-term studies. While positively charged coatings (e.g., PEI) enhance cellular uptake, they may increase cytotoxicity compared to neutral or negatively charged coatings (e.g., PAA, PEG). Dissolution of UCNPs releasing rare-earth and fluoride ions contributes to dark toxicity, but biocompatible shells (silica, PEG) reduce this effect. Overall, UCNPs demonstrate favorable biocompatibility at established doses, supporting their continued development for in vivo theranostic applications. This review is the first of three parts; subsequent parts address phototoxicity and toxicity of multimodal particles.