Intracellular Adenosine Triphosphate Deprivation through Lanthanide-Doped Nanoparticles.
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.
†Laboratory of Advanced Materials, Fudan University, Shanghai 200433, China.|‡Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
Jing
J
Tian
‡Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
Xiao
X
Zeng
‡Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
Xiaoji
X
Xie
‡Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
Sanyang
S
Han
§Cardiovascular Research Institute, Department of Medicine, National University of Singapore, National University Health System, Singapore 117599, Singapore.
Oi-Wah
OW
Liew
§Cardiovascular Research Institute, Department of Medicine, National University of Singapore, National University Health System, Singapore 117599, Singapore.
Yei-Tsung
YT
Chen
†Laboratory of Advanced Materials, Fudan University, Shanghai 200433, China.
Lianhui
L
Wang
‡Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.|⊥Institute of Materials Research and Engineering, 3 Research Link, Singapore 117602, Singapore.
Xiaogang
X
Liu
D000255:Adenosine Triphosphate / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D028581:Lanthanoid Series Elements / Q000737:chemistry / Q000494:pharmacology*; D053768:Metal Nanoparticles / Q000737:chemistry*; D013329:Structure-Activity Relationship
D028581:Lanthanoid Series Elements; D000255:Adenosine Triphosphate