Nano Research

, Volume 10, Issue 10, pp 3269–3284 | Cite as

Surface chemistry of carbon nanoparticles functionally select their uptake in various stages of cancer cells

  • Indrajit Srivastava
  • Santosh K. Misra
  • Fatemeh Ostadhossein
  • Enrique Daza
  • Jasleena Singh
  • Dipanjan Pan
Research Article

Abstract

Relationship of the surface physicochemical characteristics of nanoparticles with their interactions with biological entities may provide critical information for nanomedicinal application. Here, we report the systematic synthesis of sub-50 nm carbon nanoparticles (CNP) presenting neutral, anionic, and cationic surface functionalities. A subset of CNPs with ~10, 20, and 40 nm hydrodynamic sizes were synthesized with neutral surface headgroups. For the first time, the cellular internalization of these CNPs was systematically quantified in various stages of breast cancer cells (early, late, and metastatic), thereby providing a parametric assessment of charge and size effects. Distinct activities were observed when these systems interacted with cancer cells in various stages. Our results indicated that metastatic breast cancer could be targeted by a nanosystem presenting anionic phosphate groups. On the contrary, for patients in late stage of cancer, drugs could be delivered with sulfonate functionalized carbon nanoparticles, which have higher probability of intracellular transport. This study will facilitate the better understanding of nanoparticle–biological entity interaction, and the integration of this knowledge with pathophysiology would promote the engineering of nanomedicine with superior likelihoods of crossing the endocytic “barrier” for drug delivery inside cancerous cells.

Keywords

personalized medicine endocytosis surface charge size carbon nanoparticles 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

12274_2017_1518_MOESM1_ESM.pdf (4.1 mb)
Surface chemistry of carbon nanoparticles functionally select their uptake in various stages of cancer cells

References

  1. [1]
    Anselmo, A. C.; Mitragotri, S. Nanoparticles in the clinic. Bioengineer. Translat. Med. 2016, 1, 10–29.CrossRefGoogle Scholar
  2. [2]
    Eifler, A. C.; Thaxton, C. S. Nanoparticle therapeutics: FDA approval, clinical trials, regulatory pathways, and case study. In Biomedical Nanotechnology; Hurst, S. J., Ed.; Humana Press: New York,2011; pp 325–338.CrossRefGoogle Scholar
  3. [3]
    Ferrari, M. Cancer nanotechnology: Opportunities and challenges. Nat. Rev. Cancer 2005, 5, 161–171.CrossRefGoogle Scholar
  4. [4]
    Youan, B. B. C. Impact of nanoscience and nanotechnology on controlled drug delivery. Nanomedicine 2008, 3, 401–406.CrossRefGoogle Scholar
  5. [5]
    Farokhzad, O. C.; Langer, R. Impact of nanotechnology on drug delivery. ACS Nano 2009, 3, 16–20.CrossRefGoogle Scholar
  6. [6]
    Brigger, I.; Dubernet, C.; Couvreur, P. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Deliv. Rev. 2012, 64, 24–36.CrossRefGoogle Scholar
  7. [7]
    Wang, T. T.; Bai, J.; Jiang, X. E.; Nienhaus, G. U. Cellular uptake of nanoparticles by membrane penetration: A study combining confocal microscopy with FTIR spectroelectrochemistry. ACS Nano 2012, 6, 1251–1259.CrossRefGoogle Scholar
  8. [8]
    Vercauteren, D.; Vandenbroucke, R. E.; Jones, A. T.; Rejman, J.; Demeester, J.; De Smedt, S. C.; Sanders, N. N.; Braeckmans, K. The use of inhibitors to study endocytic pathways of gene carriers: Optimization and pitfalls. Mol. Ther. 2010, 18, 561–569.CrossRefGoogle Scholar
  9. [9]
    Chen, X. M.; Tian, F. L.; Zhang, X. R.; Wang, W. C. Internalization pathways of nanoparticles and their interaction with a vesicle. Soft Matter 2013, 9, 7592–7600.CrossRefGoogle Scholar
  10. [10]
    Doherty, G. J.; McMahon, H. T. Mechanisms of endocytosis. Annu. Rev. Biochem. 2009, 78, 857–902.CrossRefGoogle Scholar
  11. [11]
    Ivanov, A. I. Pharmacological inhibition of endocytic pathways: Is it specific enough to be useful? In Exocytosis and Endocytosis: Methods in Molecular Biology; Ivanov, A. I., Ed.; Humana Press: New York,2008; pp 15–33.CrossRefGoogle Scholar
  12. [12]
    Conner, S. D.; Schmid, S. L. Regulated portals of entry into the cell. Nature 2003, 422, 37–44.CrossRefGoogle Scholar
  13. [13]
    Swanson, J. A.; Watts, C. Macropinocytosis. Trends Cell Biol. 1995, 5, 424–428.CrossRefGoogle Scholar
  14. [14]
    Kumari, S.; Mg, S.; Mayor, S. Endocytosis unplugged: Multiple ways to enter the cell. Cell Res. 2010, 20, 256–275.CrossRefGoogle Scholar
  15. [15]
    Lundqvist, M.; Stigler, J.; Elia, G.; Lynch, I.; Cedervall, T.; Dawson, K. A. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc. Natl. Acad. Sci. USA 2008, 105, 14265–14270.CrossRefGoogle Scholar
  16. [16]
    Zhang, S. L.; Li, J.; Lykotrafitis, G.; Bao, G.; Suresh, S. Size-dependent endocytosis of nanoparticles. Adv. Mater. 2009, 21, 419–424.CrossRefGoogle Scholar
  17. [17]
    Walkey, C. D.; Olsen, J. B.; Guo, H. B.; Emili, A.; Chan, W. C. W. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J. Am. Chem. Soc. 2012, 134, 2139–2147.CrossRefGoogle Scholar
  18. [18]
    Saha, K.; Kim, S. T.; Yan, B.; Miranda, O. R.; Alfonso, F. S.; Shlosman, D.; Rotello, V. M. Surface functionality of nanoparticles determines cellular uptake mechanisms in mammalian cells. Small 2013, 9, 300–305.CrossRefGoogle Scholar
  19. [19]
    Kostarelos, K.; Lacerda, L.; Pastorin, G.; Wi, W.; Wieckowski, S.; Luangsivilay, J.; Godefroy, S.; Pantarotto, D.; Briand, J. P.; Muller, S. et al. Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type. Nat. Nanotechnol. 2007, 2, 108–113.CrossRefGoogle Scholar
  20. [20]
    Liang, M. T.; Lin, I. C.; Whittaker, M. R.; Minchin, R. F.; Monteiro, M. J.; Toth, I. Cellular uptake of densely packed polymer coatings on gold nanoparticles. ACS Nano 2010, 4, 403–413.CrossRefGoogle Scholar
  21. [21]
    Arvizo, R. R.; Rana, S.; Miranda, O. R.; Bhattacharya, R.; Rotello, V. M.; Mukherjee, P. Mechanism of anti-angiogenic property of gold nanoparticles: Role of nanoparticle size and surface charge. Nanomedicine 2011, 7, 580–587.CrossRefGoogle Scholar
  22. [22]
    Cho, E. C.; Xie, J. W.; Wurm, P. A.; Xia, Y. N. Understanding the role of surface charges in cellular adsorption versus internalization by selectively removing gold nanoparticles on the cell surface with a I2/KI etchant. Nano Lett. 2009, 9, 1080–1084.CrossRefGoogle Scholar
  23. [23]
    Liu, Z.; Liang, X. J. Nano-carbons as theranostics. Theranostics 2012, 2, 235–237.CrossRefGoogle Scholar
  24. [24]
    Qin, W.; Ding, D.; Liu, J. Z.; Yuan, W. Z.; Hu, Y.; Liu, B.; Tang, B. Z. Biocompatible nanoparticles with aggregationinduced emission characteristics as far-red/near-infrared fluorescent bioprobes for in vitro and in vivo imaging applications. Adv. Funct. Mater. 2012, 22, 771–779.CrossRefGoogle Scholar
  25. [25]
    Misra, S. K.; Chang, H. H.; Mukherjee, P.; Tiwari, S.; Ohoka, A.; Pan, D. Regulating biocompatibility of carbon spheres via defined nanoscale chemistry and a careful selection of surface functionalities. Sci. Rep. 2015, 5, 14986.CrossRefGoogle Scholar
  26. [26]
    Ferrari, A. C.; Roberston, J. Raman spectroscopy of amorphous, nanostructured, diamond-like carbon, and nanodiamond. Phil. Trans. Roy. Soc. A 2004, 362, 2477–2512.CrossRefGoogle Scholar
  27. [27]
    Mahou, R.; Wandrey, C. Versatile route to synthesize heterobifunctional poly(ethylene glycol) of variable functionality for subsequent pegylation. Polymers 2012, 4, 561–589.CrossRefGoogle Scholar
  28. [28]
    Gliem, M.; Heupel, W.-M.; Spindler, V.; Harms, G. S.; Waschke, J. Actin reorganization contributes to loss of cell adhesion in pemphigus vulgaris. Am. J. Physiol.–Cell Physiol. 2010, 299, C606–C613.CrossRefGoogle Scholar
  29. [29]
    Papakonstanti, E. A.; Stournaras, C. Cell responses regulated by early reorganization of actin cytoskeleton. FEBS Lett. 2008, 582, 2120–2127.CrossRefGoogle Scholar
  30. [30]
    Allen, C.; Yu, Y. S.; Eisenberg, A.; Maysinger, D. Cellular internalization of PCL20-b-PEO44 block copolymer micelles. Biochim. Biophy. Acta 1999, 1421, 32–38.CrossRefGoogle Scholar
  31. [31]
    Wang, L. M.; Liu, Y.; Li, W.; Jiang, X. M.; Ji, Y. L.; Wu, X. C.; Xu, L. G.; Qiu, Y.; Zhao, K.; Wei, T. T. et al. Selective targeting of gold nanorods at the mitochondria of cancer cells: Implications for cancer therapy. Nano Lett. 2011, 11, 772–780.CrossRefGoogle Scholar
  32. [32]
    Kim, J. S.; Yoon, T. J.; Yu, K. N.; Noh, M. S.; Woo, M.; Kim, B. G.; Lee, K. H.; Sohn, B. H.; Park, S. B.; Lee, J. K., Cho, M. H. Cellular uptake of magnetic nanoparticle is mediated through energy-dependent endocytosis in A549 cells. J. Vet. Sci. 2006, 11, 772.Google Scholar
  33. [33]
    Wang, L. H.; Rothberg, K. G.; Anderson, R. G. Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation. J. Cell Biol. 1993, 123, 1107–1117.CrossRefGoogle Scholar
  34. [34]
    McMahon, H. T.; Boucrot, E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 2011, 12, 517–533.CrossRefGoogle Scholar
  35. [35]
    Stuart, A. D.; Brown, T. D. K. Entry of feline calicivirus is dependent on clathrin-mediated endocytosis and acidification in endosomes. J. Virol. 2006, 80, 7500–7509.CrossRefGoogle Scholar
  36. [36]
    Macia, E.; Ehrlich, M.; Massol, R.; Boucrot, E.; Bruneer, C.; Kirchhausen, T. Dynasore, a cell-permeable inhibitor of dynamin. Dev. Cell 2006, 10, 839–850.CrossRefGoogle Scholar
  37. [37]
    Kirchhausen, T.; Macia, E.; Pelish, H. E. Use of dynasore, the small molecule inhibitor of dynamin, in the regulation of endocytosis. Method. Enzymol. 2008, 438, 77–93.CrossRefGoogle Scholar
  38. [38]
    Chen, Y.; Wang, S.; Lu, X.; Zhang, H. R.; Fu, Y.; Luo, Y. Z. Cholesterol sequestration by nystatin enhances the uptake and activity of endostatin in endothelium via regulating distinct endocytic pathways. Blood 2011, 117, 6392–6403.CrossRefGoogle Scholar
  39. [39]
    Sigismund, J.; Woelk, T.; Puri, C.; Maspero, E.; Tacchetti, C.; Transidico, P.; Di Fiore, P. P.; Polo, S. Clathrin-independent endocytosis of ubiquitinated cargos. Proc. Natl. Acad. Sci. USA 2005, 102, 2760–2765.CrossRefGoogle Scholar
  40. [40]
    Raghu, H.; Sodadasu, P. K.; Malla, R. R.; Gondi, C. S.; Estes, N.; Rao, J. S. Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells. BMC Cancer 2010, 10, 647.CrossRefGoogle Scholar
  41. [41]
    Zhang, L. W.; Monteiro-Riviere, N. A. Mechanisms of quantum dot nanoparticle cellular uptake. Toxicol. Sci. 2009, 110, 138–155.CrossRefGoogle Scholar
  42. [42]
    Lunov, O.; Syrovets, T.; Loos, C.; Beil, J.; Delecher, M.; Tron, K.; Neinhaus, G. U.; Musyanovych, A.; Mailä nder, V.; Landfester, K. et al. Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line. ACS Nano 2011, 5, 1657–1669.CrossRefGoogle Scholar
  43. [43]
    Gratton, S. E. A.; Ropp, P. A.; Pohlhaus, P. D.; Luft, J. C.; Madden, V. J.; Napier, M. E.; DeSimone, J. M. The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. USA 2008, 105, 11613–11618.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Indrajit Srivastava
    • 1
    • 2
  • Santosh K. Misra
    • 1
    • 2
  • Fatemeh Ostadhossein
    • 1
    • 2
  • Enrique Daza
    • 1
    • 2
  • Jasleena Singh
    • 1
    • 2
  • Dipanjan Pan
    • 1
    • 2
    • 3
  1. 1.Department of BioengineeringUniversity of Illinois, Urbana-ChampaignUrbanaUSA
  2. 2.Biomedical Research CenterCarle Foundation HospitalUrbanaUSA
  3. 3.Department of Materials Science and Beckman InstituteUniversity of Illinois, Urbana-ChampaignUrbanaUSA

Personalised recommendations