Carbon Nanotubes Physicochemical Properties Influence the Overall Cellular Behavior and Fate

Overview

Journal NanoImpact

Specialties Biotechnology
Toxicology

Date 2019 Sep 24

PMID 31544167

Citations 5

Authors

Reem Eldawud

Alixandra Wagner

Chenbo Dong

Todd A Stueckle

Yon Rojanasakul

Cerasela Zoica Dinu

Affiliations

Soon will be listed here.

Abstract

The unique properties of single walled carbon nanotubes (SWCNTs) make them viable candidates for versatile implementation in the next generation of biomedical devices for targeted delivery of chemotherapeutic agents or cellular-sensing probes. Such implementation requires user-tailored changes in SWCNT's physicochemical characteristics to allow for efficient cellular integration while maintaining nanotubes' functionality. However, isolated reports showed that user-tailoring could induce deleterious effects in exposed cells, from decrease in cellular proliferation, to changes in cellular adhesion, generation of reactive oxygen species or phenotypical variations, just to name a few. Before full implementation of SWCNTs is achieved, their toxicological profiles need to be mechanistically correlated with their physicochemical properties to determine how the induced cellular fate is related to the exposure conditions or samples' characteristics. Our study provides a comprehensive analysis of the synergistic cyto- and genotoxic effects resulted from short-term exposure of human lung epithelial cells to pristine (as manufactured) and user-tailored SWCNTs, as a function of their physicochemical properties. Specifically, through a systematic approach we are correlating the nanotube uptake and nanotube-induced cellular changes to the sample's physicochemical characteristics (e.g., metal impurities, length, agglomerate size, surface area, dispersion, and surface functionalization). By identifying changes in active hallmarks involved in cell-cell connections and maintaining epithelial layer integrity, we also determine the role that short-term exposure to SWCNTs plays in the overall cellular fate and cellular transformation. Lastly, we assess cellular structure-function relationships to identify non-apoptotic pathways induced by SWCNTs exposure that could however lead to changes in cellular behavior and cellular transformation. Our results show that the degree of cell transformation is a function of the physicochemical properties of the SWCNT, with the nanotube with higher length, higher metal content and larger agglomerate size reducing cell viability to a larger extent. Such changes in cell viability are also complemented by changes in cell structure, cycle and cell-cell interactions, all responsible for maintaining cell fate.

Citing Articles

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References

Levesque J, Simmons P . Cytoskeleton and integrin-mediated adhesion signaling in human CD34+ hemopoietic progenitor cells. Exp Hematol. 1999; 27(4):579-86. DOI: 10.1016/s0301-472x(98)00069-1. View

Wiebe J, Muzia D, Hu J, Szwajcer D, Hill S, Seachrist J . The 4-pregnene and 5alpha-pregnane progesterone metabolites formed in nontumorous and tumorous breast tissue have opposite effects on breast cell proliferation and adhesion. Cancer Res. 2000; 60(4):936-43. View

Pawlak G, Helfman D . Cytoskeletal changes in cell transformation and tumorigenesis. Curr Opin Genet Dev. 2001; 11(1):41-7. DOI: 10.1016/s0959-437x(00)00154-4. View

Lee S, Song E, Kim H, Kang H, Kim J, Lee K . Rac1 regulates heat shock responses by reorganization of vimentin filaments: identification using MALDI-TOF MS. Cell Death Differ. 2001; 8(11):1093-102. DOI: 10.1038/sj.cdd.4400923. View

Ridley A . Rho family proteins: coordinating cell responses. Trends Cell Biol. 2001; 11(12):471-7. DOI: 10.1016/s0962-8924(01)02153-5. View

Palacios F, Schweitzer J, Boshans R, DSouza-Schorey C . ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly. Nat Cell Biol. 2002; 4(12):929-36. DOI: 10.1038/ncb881. View

Pecina-Slaus N . Tumor suppressor gene E-cadherin and its role in normal and malignant cells. Cancer Cell Int. 2003; 3(1):17. PMC: 270068. DOI: 10.1186/1475-2867-3-17. View

Maynard A, Baron P, Foley M, Shvedova A, Kisin E, Castranova V . Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material. J Toxicol Environ Health A. 2003; 67(1):87-107. DOI: 10.1080/15287390490253688. View

Gotzmann J, Mikula M, Eger A, Schulte-Hermann R, Foisner R, Beug H . Molecular aspects of epithelial cell plasticity: implications for local tumor invasion and metastasis. Mutat Res. 2004; 566(1):9-20. DOI: 10.1016/s1383-5742(03)00033-4. View

10.

Aznar S, Fernandez-Valeron P, Espina C, Lacal J . Rho GTPases: potential candidates for anticancer therapy. Cancer Lett. 2004; 206(2):181-91. DOI: 10.1016/j.canlet.2003.08.035. View

11.

Izumi G, Sakisaka T, Baba T, Tanaka S, Morimoto K, Takai Y . Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through IQGAP1 and actin filaments. J Cell Biol. 2004; 166(2):237-48. PMC: 2172308. DOI: 10.1083/jcb.200401078. View

12.

Campisi J . Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005; 120(4):513-22. DOI: 10.1016/j.cell.2005.02.003. View

13.

Dalton S . Cell cycle regulation of the human cdc2 gene. EMBO J. 1992; 11(5):1797-804. PMC: 556637. DOI: 10.1002/j.1460-2075.1992.tb05231.x. View

14.

Kam N, Liu Z, Dai H . Carbon nanotubes as intracellular transporters for proteins and DNA: an investigation of the uptake mechanism and pathway. Angew Chem Int Ed Engl. 2005; 45(4):577-81. DOI: 10.1002/anie.200503389. View

15.

Kagan V, Tyurina Y, Tyurin V, Konduru N, Potapovich A, Osipov A . Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. Toxicol Lett. 2006; 165(1):88-100. DOI: 10.1016/j.toxlet.2006.02.001. View

16.

Tian F, Cui D, Schwarz H, Estrada G, Kobayashi H . Cytotoxicity of single-wall carbon nanotubes on human fibroblasts. Toxicol In Vitro. 2006; 20(7):1202-12. DOI: 10.1016/j.tiv.2006.03.008. View

17.

Fernandez-Vidal A, Ysebaert L, Didier C, Betous R, De Toni F, Prade-Houdellier N . Cell adhesion regulates CDC25A expression and proliferation in acute myeloid leukemia. Cancer Res. 2006; 66(14):7128-35. DOI: 10.1158/0008-5472.CAN-05-2552. View

18.

Mallette F, Gaumont-Leclerc M, Ferbeyre G . The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes Dev. 2007; 21(1):43-8. PMC: 1759898. DOI: 10.1101/gad.1487307. View

19.

Pumera M . Carbon nanotubes contain residual metal catalyst nanoparticles even after washing with nitric acid at elevated temperature because these metal nanoparticles are sheathed by several graphene sheets. Langmuir. 2007; 23(11):6453-8. DOI: 10.1021/la070088v. View

20.

McInroy L, Maatta A . Down-regulation of vimentin expression inhibits carcinoma cell migration and adhesion. Biochem Biophys Res Commun. 2007; 360(1):109-14. DOI: 10.1016/j.bbrc.2007.06.036. View