title: Selective killing of hepatocellular carcinoma HepG2 cells by three-dimensional nanographene nanoparticles based on triptycene.
abstract: Carbon-based materials have been widely used in the biomedical fields including drug delivery and cancer therapies. In this paper, a recently synthesized three-dimensional nanographene (NG) based on triptycene self-assembles into nanoparticles which selectively kill human hepatocellular carcinoma HepG2 cells as compared to human normal liver HL7702 cells. Obvious differences in cellular accumulation, the endocytic pathway and intracellular trafficking of NG nanoparticles are observed in HepG2 cells and HL7702 cells. Further studies reveal that NG nanoparticles significantly increase the levels of reactive oxygen species (ROS) in HepG2 cells, but not in HL7702 cells. NG nanoparticle-induced ROS result in apoptosis induction and the decrease in mitochondrial membrane potential in HepG2 cells. Moreover, IKK/nuclear factor-κB (NF-κB) signaling is found to be activated by NG nanoparticle-induced ROS and serves to antagonize NG nanoparticle-induced apoptosis in HepG2 cells. Our studies show that the distinct behaviors of cellular uptake and ROS-mediated cytotoxicity are responsible for the selective killing of HepG2 cells. This study provides a foundation for understanding the mechanism of selective induction of apoptosis in cancer cells by NG nanoparticles and designing more effective chemotherapeutical agents.
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. lugan@mail.hust.edu.cn chunzhang@mail.hust.edu.cn yangxl@mail.hust.edu.cn.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Xiong
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Tuying
authors.initials: T
authors.lastname: Yong
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Wang
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000873:Anthracenes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D006108:Graphite; D056945:Hep G2 Cells; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D017382:Reactive Oxygen Species; D006108:Graphite; C520712:triptycene