†Laboratory of Advanced Materials, Fudan University, Shanghai 200433, China.
‡Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
J Am Chem Soc. 2015 May 27;137(20):6550-8. doi: 10.1021/jacs.5b00981. Epub 2015 May 14.
Growing interest in lanthanide-doped nanoparticles for biological and medical uses has brought particular attention to their safety concerns. However, the intrinsic toxicity of this new class of optical nanomaterials in biological systems has not been fully evaluated. In this work, we systematically evaluate the long-term cytotoxicity of lanthanide-doped nanoparticles (NaGdF4 and NaYF4) to HeLa cells by monitoring cell viability (mitochondrial activity), adenosine triphosphate (ATP) level, and cell membrane integrity (lactate dehydrogenase release), respectively. Importantly, we find that ligand-free lanthanide-doped nanoparticles induce intracellular ATP deprivation of HeLa cells, resulting in a significant decrease in cell viability after exposure for 7 days. We attribute the particle-induced cell death to two distinct cell death pathways, autophagy and apoptosis, which are primarily mediated via the interaction between the nanoparticle and the phosphate group of cellular ATP. The understanding gained from the investigation of cytotoxicity associated with lanthanide-doped nanoparticles provides keen insights into the safe use of these nanoparticles in biological systems.
人们对镧系掺杂纳米粒子在生物和医学方面的应用越来越感兴趣，这引起了人们对其安全性的关注。然而，这类新型光学纳米材料在生物系统中的固有毒性尚未得到充分评估。在这项工作中，我们通过分别监测细胞活力（线粒体活性）、三磷酸腺苷（ATP）水平和细胞膜完整性（乳酸脱氢酶释放），系统地评估了镧系掺杂纳米粒子（NaGdF4 和 NaYF4）对 HeLa 细胞的长期细胞毒性。重要的是，我们发现无配体的镧系掺杂纳米粒子会导致 HeLa 细胞内的 ATP 耗竭，从而导致暴露 7 天后细胞活力显著下降。我们将颗粒诱导的细胞死亡归因于两种不同的细胞死亡途径，自噬和细胞凋亡，这主要是通过纳米颗粒与细胞 ATP 的磷酸基团相互作用介导的。从对镧系掺杂纳米粒子相关细胞毒性的研究中获得的认识，为这些纳米粒子在生物系统中的安全应用提供了深刻的见解。
