稀土掺杂上转换纳米颗粒（UCNPs）的生物学毒性效应以及对环境和人类健康的影响成为新的研究热点，其毒性机制尚未明确。纳米颗粒的生物学毒性与其在生物体内的形态变化密切相关。本项目针对UCNPs不同形态分离分析中的技术难点，将毛细管电泳（CE）或尺寸排阻高效液相色谱（SEC-HPLC）与电感耦合等离子体质谱（ICP-MS）联用，优化色谱分离和质谱测定条件，实现复杂生物体系中不同形态UCNPs的分离分析，同时进行方法学性能评价，建立高灵敏度、低检出限的基于CE（SEC-HPLC）-ICP-MS联用技术的生物体系中UCNPs形态分析新技术。通过细胞和动物实验明确UCNPs对细胞增殖、DNA损伤、动物组织病理、肝/肾组织抗氧化酶系等的损伤作用，建立UCNPs不同形态与其生物学效应/毒性之间的相关性，探讨UCNPs对生物蓄积、排泄和靶器官生理功能的影响，为阐明UCNPs的生物毒性机制提供关键技术支撑。

The impact of rare-earth-doped upconversion nanoparticles (UCNPs) on environment and human health, especially their biological toxicity, have become a new research hotspot. However, the toxicity mechanism of UCNPs has not yet been clarified. The biological toxicity of nanoparticles is closely related to their speciation changes in vivo and in vitro. In view of the difficulties of speciation analysis of UCNPs, a combination of capillary electrophoresis (CE) or size exclusion high performance liquid chromatography (SEC-HPLC) and inductively coupled plasma mass spectrometry (ICP-MS) is used to separate and analyze different speciation of UCNPs in complex biological systems by optimizing the conditions for chromatographic separation and ICP-MS detection, then the methodological performance will be evaluated. A new technique for speciation analysis of UCNPs based on CE (SEC-HPLC) -ICP-MS with high sensitivity and low detection limit will be established. Through cell and animal experiments, the effects of different speciation of UCNPs on cell proliferation, DNA damage, animal histopathology, liver/kidney antioxidant enzymes and so on is identified. Based on the above, the correlation between different speciation of UCNPs and their biological effects/toxicity is established. This study will provide the key technical support for the further study of the effects of UCNPs on biological accumulation, excretion and physiological functions of target organs and the clarification of the biological toxicity mechanism of UCNPs.