title: Cytotoxic effects of cytoplasmic-targeted and nuclear-targeted gold and silver nanoparticles in HSC-3 cells--a mechanistic study.
abstract: Nanoparticles (NPs), in particular noble metal nanoparticles, have been incorporated into many therapeutic and biodiagnostic applications. While these particles have many advantageous physical and optical properties, little is known about their intrinsic intracellular effects in biological environments. Here, we report the possible cell death mechanisms triggered in human oral squamous cell carcinoma (HSC-3) cells after exposure to extracellular, cytoplasm, and nuclear localized AuNPs and AgNPs. NP uptake and localization, cell viability, ATP levels, modes of cell death, ROS generation, mitochondrial depolarization, and the levels and/or translocation of caspase-dependent and caspase-independent proteins were assessed under control and localized metal nanoparticle exposure. Exposure to AuNPs resulted the adoption of a quiescent cellular state, as AuNPs caused a decrease in intracellular ATP, but no change in viability or cell death populations. However, AgNP exposure significantly reduced HSC-3 cell viability and increased apoptotic populations, especially when localized at the cytoplasm and nucleus. Increased cell death populations were linked to an increase in intracellular ROS generation. Western blot analysis indicated cytoplasm localized AgNPs and nuclear localized AgNPs utilized a caspase-independent apoptotic pathway that involved the nuclear translocation of AIF and p38 MAPK proteins. These results demonstrate that the degree of cytotoxicity increases as AgNPs move from extracellular localization to nuclear localization, whereas changing AuNP localization does not trigger any significant cytotoxicity.
authors.affiliation: Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Austin
authors.affiliation: Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
authors.forename: Samera
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Present Address: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 210093, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Kang
authors.affiliation: Parker H. Petit Institute for Bioengineering and Biosciences, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Rommel
authors.affiliation: Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mahmoud
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332-0400, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Peek
authors.affiliation: Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA. Electronic address: melsayed@gatech.edu.
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: El-Sayed
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects*; D006046:Gold / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D009336:Necrosis; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*
chemical_list: D010455:Peptides; D017382:Reactive Oxygen Species; D012834:Silver; D011092:Polyethylene Glycols; D006046:Gold; D020169:Caspases
keywords: Apoptosis; Cytotoxicity; Gold nanoparticles; Organelle-targeted nanoparticles; Silver nanoparticles