Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Understanding biophysicochemical interactions at the nano–bio interface

Abstract

Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes. For their part, the biomolecules may induce phase transformations, free energy releases, restructuring and dissolution at the nanomaterial surface. Probing these various interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings. This knowledge is important from the perspective of safe use of nanomaterials.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Representation of the interface between a nanoparticle and a lipid bilayer.
Figure 2: Interactions between nanoparticles.
Figure 3: Effects of protein corona surrounding a nanoparticle.
Figure 4: Nanoparticle wrapping at the surface membrane.
Figure 5: Representation of receptor-mediated uptake.
Figure 6: Schematic of the proton sponge effect leading to lysosomal damage and the induction of cytotoxicity by cationic nanoparticles.
Figure 7: Influence of ZnO on lysosomal function.
Figure 8: Physical characteristics of nanoparticles determine in vivo biocompatibility.

Similar content being viewed by others

References

  1. Nel, A., Xia, T., Madler, L. & Li, N. Toxic potential of materials at the nanolevel. Science 311, 622–627 (2006).

    CAS  Google Scholar 

  2. Oberdorster, G. et al. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part. Fibre Toxicol. 2, 8 (2005).

    Google Scholar 

  3. Vertegel, A. A., Siegel, R. W. & Dordick, J. S. Silica nanoparticle size influences the structure and enzymatic activity of adsorbed lysozyme. Langmuir 20, 6800–6807 (2004).

    CAS  Google Scholar 

  4. Sigmund, W., Pyrgiotakis, G. & Daga, A. Chemical Processing of Ceramics (CRC, 2005).

    Google Scholar 

  5. Gilbert, B., Huang, F., Zhang, H., Waychunas, G. A. & Banfield, J. F. Nanoparticles: Strained and stiff. Science 305, 651–654 (2004).

    CAS  Google Scholar 

  6. Min, Y., Akbulut, M., Kristiansen, K., Golan, Y. & Israelachvili, J. The role of interparticle and external forces in nanoparticle assembly. Nature Mater. 7, 527–538 (2008).

    CAS  Google Scholar 

  7. Velegol, D. Assembling colloidal devices by controlling interparticle forces. J. Nanophoton. 1, 012502 (2007).

    Google Scholar 

  8. Baca, H. K. et al. Cell-directed assembly of lipid–silica nanostructures providing extended cell viability. Science 313, 337–341 (2006).

    CAS  Google Scholar 

  9. Dagastine, R. R. et al. Dynamic forces between two deformable oil droplets in water. Science 313, 210–213 (2006).

    CAS  Google Scholar 

  10. Kim, H. Y., Sofo, J. O., Velegol, D., Cole, M. W. & Lucas, A. A. Van der Waals dispersion forces between dielectric nanoclusters. Langmuir 23, 1735–1740 (2007).

    CAS  Google Scholar 

  11. Feick, J. D., Chukwumah, N., Noel, A. E. & Velegol, D. Altering surface charge nonuniformity on individual colloidal particles. Langmuir 20, 3090–3095 (2004).

    CAS  Google Scholar 

  12. Velegol, D. & Thwar, P. K. Analytical model for the effect of surface charge nonuniformity on colloidal interactions. Langmuir 17, 7687–7693 (2001).

    CAS  Google Scholar 

  13. Baca, H. K. et al. Cell-directed assembly of bio/nano interfaces: A new scheme for cell immobilization. Acc. Chem. Res. 40, 836–845 (2007).

    CAS  Google Scholar 

  14. Dobrovolskaia, M. A. & McNeil, S. E. Immunological properties of engineered nanomaterials. Nature Nanotech. 2, 469–478 (2007).

    CAS  Google Scholar 

  15. Swanson, J. A. Shaping cups into phagosomes and macropinosomes. Nature Rev. Mol. Cell Biol. 9, 639–649 (2008).

    CAS  Google Scholar 

  16. Chen, H., Langer, R. & Edwards, D. A. A film tension theory of phagocytosis. J. Colloid Interface Sci. 190, 118–133 (1997).

    CAS  Google Scholar 

  17. Cedervall, T. et al. Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc. Natl Acad. Sci. USA 104, 2050–2055 (2007).

    CAS  Google Scholar 

  18. Linse, S. et al. Nucleation of protein fibrillation by nanoparticles. Proc. Natl Acad. Sci. USA 104, 8691–8696 (2007).

    CAS  Google Scholar 

  19. Lundqvist, M. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc. Natl Acad. Sci. USA 105, 14265–14270 (2008).

    CAS  Google Scholar 

  20. Owens, D. E. III & Peppas, N. A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 307, 93–102 (2006).

    CAS  Google Scholar 

  21. Xia, T. et al. Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. Am. Chem. Soc. Nano 2, 2121–2134 (2008).

    CAS  Google Scholar 

  22. Rodriguez, C. E., Fukuto, J. M., Taguchi, K., Froines, J. & Cho, A. K. The interactions of 9,10-phenanthrenequinone with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a potential site for toxic actions. Chem. Biol. Interact. 155, 97–110 (2005).

    CAS  Google Scholar 

  23. Decuzzi, P. & Ferrari, M. The role of specific and nonspecific interactions in receptor-mediated endocytosis of nanoparticles. Biomaterials 28, 2915–2922 (2007).

    CAS  Google Scholar 

  24. Gao, H., Shi, W. & Freund, L. B. Mechanics of receptor-mediated endocytosis. Proc. Natl Acad. Sci. USA 102, 9469–9474 (2005).

    CAS  Google Scholar 

  25. Chithrani, B. D. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 6, 662–668 (2006).

    CAS  Google Scholar 

  26. Verma, A. et al. Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. Nature Mater. 7, 588–595 (2008).

    CAS  Google Scholar 

  27. Fernandez-Carneado, J., Kogan, M. J., Pujals, S. & Giralt, E. Amphipathic peptides and drug delivery. Biopolymers 76, 196–203 (2004).

    CAS  Google Scholar 

  28. Leroueil, P. R. Wide varieties of cationic nanoparticles induce defects in supported lipid bilayers. Nano Lett. 8, 420–424 (2008).

    CAS  Google Scholar 

  29. Fleck, C. C. & Netz, R. R. Electrostatic colloid-membrane binding. Europhys. Lett. 67, 314–320 (2004).

    CAS  Google Scholar 

  30. Wong-Ekkabut, J. et al. Computer simulation study of fullerene translocation through lipid membranes. Nature Nanotech. 3, 363–368 (2008).

    CAS  Google Scholar 

  31. Vonarbourg, A., Passirani, C., Saulnier, P. & Benoit, J. P. Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 27, 4356–4373 (2006).

    CAS  Google Scholar 

  32. Hoek, E. M. & Agarwal, G. K. Extended DLVO interactions between spherical particles and rough surfaces. J. Colloid Interface Sci. 298, 50–58 (2006).

    CAS  Google Scholar 

  33. Chithrani, B. D. & Chan, W. C. Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett. 7, 1542–1550 (2007).

    CAS  Google Scholar 

  34. Qian, Z. M., Li, H., Sun, H. & Ho, K. Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol. Rev. 54, 561–587 (2002).

    CAS  Google Scholar 

  35. Gratton, S. E. et al. The effect of particle design on cellular internalization pathways. Proc. Natl Acad. Sci. USA 105, 11613–11618 (2008).

    CAS  Google Scholar 

  36. Poland, C. A. et al. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nature Nanotech. 3, 423–428 (2008).

    CAS  Google Scholar 

  37. Ferrari, M. Nanogeometry: Beyond drug delivery. Nature Nanotech. 3, 131–132 (2008).

    CAS  Google Scholar 

  38. Rejman, J., Oberle, V., Zuhorn, I. S. & Hoekstra, D. Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem. J. 377, 159–169 (2004).

    CAS  Google Scholar 

  39. Sieczkarski, S. B. & Whittaker, G. R. Dissecting virus entry via endocytosis. J. Gen. Virol. 83, 1535–1545 (2002).

    CAS  Google Scholar 

  40. Oberdorster, G., Oberdorster, E. & Oberdorster, J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113, 823–839 (2005).

    CAS  Google Scholar 

  41. Sager, T. M. et al. Improved method to disperse nanoparticles for in vitro and in vivo investigation of toxicity. Nanotoxicology 1, 118–129 (2007).

    CAS  Google Scholar 

  42. Jiang, J., Oberdorster, G. & Biswas, P. Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies. J. Nanopart. Res. 11, 77–89 (2008).

    Google Scholar 

  43. Moreau, J. W. et al. Extracellular proteins limit the dispersal of biogenic nanoparticles. Science 316, 1600–1603 (2007).

    CAS  Google Scholar 

  44. Buford, M. C., Hamilton, R. F. Jr & Holian, A. A comparison of dispersing media for various engineered carbon nanoparticles. Part. Fibre Toxicol. 4, 6 (2007).

    Google Scholar 

  45. Dutta, D. et al. Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. Toxicol. Sci. 100, 303–315 (2007).

    CAS  Google Scholar 

  46. Xia, T., Kovochich, M., Liong, M., Zink, J. I. & Nel, A. E. Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. Am. Chem. Soc. Nano 2, 85–96 (2008).

    CAS  Google Scholar 

  47. Xia, T. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett. 6, 1794–1807 (2006).

    CAS  Google Scholar 

  48. Thomas, M. & Klibanov, A. M. Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells. Proc. Natl Acad. Sci. USA 100, 9138–9143 (2003).

    CAS  Google Scholar 

  49. Kuschner, W. G. et al. Pulmonary responses to purified zinc oxide fume. J. Invest. Med. 43, 371–378 (1995).

    CAS  Google Scholar 

  50. Mercer, R. R. et al. Alteration of deposition pattern and pulmonary response as a result of improved dispersion of aspirated single-walled carbon nanotubes in a mouse model. Am. J. Physiol. Lung Cell Mol. Physiol. 294, L87–L97 (2008).

    CAS  Google Scholar 

  51. Shvedova, A. A. et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am. J. Physiol. Lung Cell Mol. Physiol. 289, L698–L708 (2005).

    CAS  Google Scholar 

  52. Monteiller, C. et al. The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: The role of surface area. Occup. Environ. Med. 64, 609–615 (2007).

    CAS  Google Scholar 

  53. Warheit, D. B., Webb, T. R., Sayes, C. M., Colvin, V. L. & Reed, K. L. Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: Toxicity is not dependent upon particle size and surface area. Toxicol. Sci. 91, 227–236 (2006).

    CAS  Google Scholar 

  54. Shvedova, A. A. et al. Nanotechnology: Characterization, Dosing and Health Effects (Informa Healthcare, 2007).

    Google Scholar 

  55. Araujo, J. A. et al. Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress. Circ. Res. 102, 589–596 (2008).

    CAS  Google Scholar 

  56. Li, N. et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ. Health Perspect. 111, 455–460 (2003).

    CAS  Google Scholar 

  57. McNeil, S. E. Nanoparticle therapeutics: A personal perspective. WIREs Nanomed. Nanobiotechnol. 1, 264–271 (2009).

    CAS  Google Scholar 

  58. Mortensen, L. J., Oberdorster, G., Pentland, A. P. & Delouise, L. A. In vivo skin penetration of quantum dot nanoparticles in the murine model: The effect of UVR. Nano Lett. 8, 2779–2787 (2008).

    CAS  Google Scholar 

  59. Goodman, C. M., McCusker, C. D., Yilmaz, T. & Rotello, V. M. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug. Chem. 15, 897–900 (2004).

    CAS  Google Scholar 

  60. Hoet, P. H., Gilissen, L. & Nemery, B. Polyanions protect against the in vitro pulmonary toxicity of polycationic paint components associated with the Ardystil syndrome. Toxicol. Appl. Pharmacol. 175, 184–190 (2001).

    CAS  Google Scholar 

  61. Lee, W. A. et al. Multicomponent polymer coating to block photocatalytic activity of TiO2 nanoparticles. Chem. Commun. 4815–4817 (2007).

  62. Vevers, W. F. & Jha, A. N. Genotoxic and cytotoxic potential of titanium dioxide (TiO2) nanoparticles on fish cells in vitro. Ecotoxicology 17, 410–420 (2008).

    CAS  Google Scholar 

  63. Hussain, S. M., Hess, K. L., Gearhart, J. M., Geiss, K. T. & Schlager, J. J. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol. In Vitro 19, 975–983 (2005).

    CAS  Google Scholar 

  64. Navarro, E. et al. Environmental behavior and ecotoxicity of engineered nanoparticles to algae, plants, and fungi. Ecotoxicology 17, 372–386 (2008).

    CAS  Google Scholar 

  65. Hauck, T. S., Ghazani, A. A. & Chan, W. C. Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. Small 4, 153–159 (2008).

    CAS  Google Scholar 

  66. Khan, J. A., Pillai, B., Das, T. K., Singh, Y. & Maiti, S. Molecular effects of uptake of gold nanoparticles in HeLa cells. ChemBioChem. 8, 1237–1240 (2007).

    CAS  Google Scholar 

  67. Kirchner, C. et al. Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett. 5, 331–338 (2005).

    CAS  Google Scholar 

  68. Ovrevik, J., Lag, M., Schwarze, P. & Refsnes, M. p38 and Src-ERK1/2 pathways regulate crystalline silica-induced chemokine release in pulmonary epithelial cells. Toxicol. Sci. 81, 480–490 (2004).

    CAS  Google Scholar 

  69. Auffan, M. et al. Relation between the redox state of iron-based nanoparticles and their cytotoxicity toward Escherichia coli. Environ. Sci. Technol. 42, 6730–6735 (2008).

    CAS  Google Scholar 

  70. Jain, T. K., Morales, M. A., Sahoo, S. K., Leslie-Pelecky, D. L. & Labhasetwar, V. Iron oxide nanoparticles for sustained delivery of anticancer agents. Mol. Pharmacol. 2, 194–205 (2005).

    CAS  Google Scholar 

  71. Laurent, S. et al. Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 108, 2064–2110 (2008).

    CAS  Google Scholar 

  72. Magrez, A. et al. Cellular toxicity of carbon-based nanomaterials. Nano Lett. 6, 1121–1125 (2006).

    CAS  Google Scholar 

  73. Carrero-Sanchez, J. C. et al. Biocompatibility and toxicological studies of carbon nanotubes doped with nitrogen. Nano Lett. 6, 1609–1616 (2006).

    CAS  Google Scholar 

  74. Kagan, V. E. et al. Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: Role of iron. Toxicol. Lett. 165, 88–100 (2006).

    CAS  Google Scholar 

  75. Lam, C. W., James, J. T., McCluskey, R. & Hunter, R. L. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol. Sci. 77, 126–134 (2004).

    CAS  Google Scholar 

  76. Sayes, C. M. et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 4, 1881–1887 (2004).

    CAS  Google Scholar 

  77. Tansey, W. et al. Synthesis and characterization of branched poly(L-glutamic acid) as a biodegradable drug carrier. J. Control Release 94, 39–51 (2004).

    CAS  Google Scholar 

  78. Guo, D. et al. In vitro cellular uptake and cytotoxic effect of functionalized nickel nanoparticles on leukemia cancer cells. J. Nanosci. Nanotech. 8, 2301–2307 (2008).

    CAS  Google Scholar 

  79. Dey, S. et al. Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells. Carcinogenesis 29, 1920–1929 (2008).

    CAS  Google Scholar 

  80. Oesterling, E. et al. Alumina nanoparticles induce expression of endothelial cell adhesion molecules. Toxicol. Lett. 178, 160–166 (2008).

    CAS  Google Scholar 

  81. Karlsson, H. L., Cronholm, P., Gustafsson, J. & Moller, L. Copper oxide nanoparticles are highly toxic: A comparison between metal oxide nanoparticles and carbon nanotubes. Chem. Res. Toxicol. 21, 1726–1732 (2008).

    CAS  Google Scholar 

  82. Chen, Z. et al. Acute toxicological effects of copper nanoparticles in vivo. Toxicol. Lett. 163, 109–120 (2006).

    CAS  Google Scholar 

  83. Niemantsverdriet, J. W. Spectroscopy in Catalysis (Wiley-VCH, 2007).

    Google Scholar 

  84. Yu, X., Jin, L. & Zhou, Z. H. 3.88 Å structure of cytoplasmic polyhedrosis virus by cryo-electron microscopy. Nature 453, 415–419 (2008).

    CAS  Google Scholar 

  85. Baumeister, W. A voyage to the inner space of cells. Protein Sci. 14, 257–269 (2005).

    CAS  Google Scholar 

  86. Carragher, B. et al. Rapid routine structure determination of macromolecular assemblies using electron microscopy: Current progress and further challenges. J. Synchrotron. Radiat. 11, 83–85 (2004).

    CAS  Google Scholar 

  87. Kaneko, K. et al. Structural and morphological characterization of cerium oxide nanocrystals prepared by hydrothermal synthesis. Nano Lett. 7, 421–425 (2007).

    CAS  Google Scholar 

  88. Porter, A. E. Direct imaging of single-walled carbon nanotubes in cells. Nature Nanotech. 2, 713–717 (2007).

    CAS  Google Scholar 

  89. Lucic, V. et al. Multiscale imaging of neurons grown in culture: from light microscopy to cryo-electron tomography. J. Struct. Biol. 160, 146–156 (2007).

    Google Scholar 

  90. Sartori, A. et al. Correlative microscopy: Bridging the gap between fluorescence light microscopy and cryo-electron tomography. J. Struct. Biol. 160, 135–145 (2007).

    Google Scholar 

  91. Steven, A. C. & Baumeister, W. The future is hybrid. J. Struct. Biol. 163, 186–195 (2008).

    CAS  Google Scholar 

  92. Heymann, J. A. et al. Site-specific 3D imaging of cells and tissues with a dual beam microscope. J. Struct. Biol. 155, 63–73 (2006).

    Google Scholar 

  93. Marko, M. Focused-ion-beam thinning of frozen-hydrated biological specimens for cryo-electron microscopy. Nature Methods 4, 215–217 (2007).

    CAS  Google Scholar 

  94. Stephens, D. J. & Allan, V. J. Light microscopy techniques for live cell imaging. Science 300, 82–86 (2003).

    CAS  Google Scholar 

  95. Qian, X. et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nature Biotechnol. 26, 83–90 (2008).

    CAS  Google Scholar 

  96. Keren, S. et al. Noninvasive molecular imaging of small living subjects using Raman spectroscopy. Proc. Natl Acad. Sci. USA 105, 5844–5849 (2008).

    CAS  Google Scholar 

  97. Liu, Z. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nature Nanotech. 2, 47–52 (2007).

    CAS  Google Scholar 

  98. Kostarelos, K. The long and short of carbon nanotube toxicity. Nature Biotechnol. 26, 774–776 (2008).

    CAS  Google Scholar 

  99. Lacerda, L. et al. Dynamic imaging of functionalized multi-walled carbon nanotube systemic circulation and urinary excretion. Adv. Mater. 20, 225–230 (2008).

    CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge support from the National Science Foundation and the Environmental Protection Agency under Cooperative Agreement Number EF 0830117. Any opinions, findings, conclusions or recommendations expressed herein are those of the author(s) and do not necessarily reflect the views of the NSF or EPA. This work has not been subjected to an EPA peer and policy review. Support for experimental work was provided by the UC Lead Campus for Nanotoxicology Training and Research, funded by UC TSR&TP, US Public Health Service grants (U19 AI070453, R01 ES016746, and RO1 ES015498) and the US EPA STAR award (RD-83241301) to the Southern California Particle Center. We are grateful for discussions and contributions provided by participants in the Biophysicochemical Interactions of Engineered Nanomaterials Workshop held at UCLA in September 2007. We thank B. Li and J. Hellmers for helping to make one of the figures and S. McNeil for providing Fig. 8.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andre E. Nel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nel, A., Mädler, L., Velegol, D. et al. Understanding biophysicochemical interactions at the nano–bio interface. Nature Mater 8, 543–557 (2009). https://doi.org/10.1038/nmat2442

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat2442

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing