Intracellular Localized Surface Plasmonic Sensing for Subcellular Diagnosis

Abstract

This paper proposes a method for diagnosing intracellular conditions and organelles of cells with localized surface plasmonic resonance (LSPR) by directly internalizing the gold nanoparticles (AuNPs) into the cells and measuring their plasmonic properties through hyperspectral imaging. This technique will be useful for direct diagnosis of cellular organelles, which have potential for cellular biology, proteomics, pharmaceuticals, drug discovery etc. Furthermore, localization and characterization of citrate-capped gold nanoparticles in HeLa cells were studied, by hyperspectral microscopy and other imaging techniques. Here, we present the method of internalizing the gold nanoparticles into the cells and subcellular organelles to facilitate subcellular plasmonic measurements. An advanced label-free visualization technique, namely hyperspectral microscopy providing images and spectral data simultaneously, was used to confirm the internalization of gold nanoparticles and to reveal their optical properties for possible intracellular plasmonic detection. Hyperspectral technology has proved to be effective in the analysis of the spectral profile of gold nanoparticles, internalized under different conditions. Using this relatively novel technique, it is possible to study the plasmonic properties of particles, localized in different parts of the cell. The position of the plasmon bands reflects the interactions of gold nanoparticles with different subcellular systems, including particle-nucleus interactions. Our results revealed the effect of the different intracellular interactions on the aggregation pattern of gold nanoparticles, inside the cells. This novel technique opens the door to intracellular plasmonics, an entirely new field, with important potential applications in life sciences. Similarly, the characterization of AuNP inside the cell was validated using traditional methods such as light microscopy and scanning electron microscopy. Under the conditions studied in this work, gold nanoparticles were found to be non-toxic to HeLa (cervical cancer) cells.

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References

  1. 1.

    Ma XX, Gong N, Zhong L, Sun J, Liang XJ (2016) Future of nanotherapeutics: targeting the cellular sub-organelles. Biomaterials 97:10–21. https://doi.org/10.1016/j.biomaterials.2016.04.026

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Hh Liu PY, Chin LK, Ser W, Chen HF, Hsieh CM, Lee CH, Sung K-B, Ayi TC, Yap PH, Liedberg B, Wang K, Bourouina T, Leprince-Wang Y (2016) Cell refractive index for cell biology and disease diagnosis: past, present and future. Lab Chip 16(4):634–644. https://doi.org/10.1039/c5lc01445j

    Article  Google Scholar 

  3. 3.

    Rajendran L, Knolker HJ, Simons K (2010) Subcellular targeting strategies for drug design and delivery. Nat Rev Drug Discov 9(1):29–42. https://doi.org/10.1038/nrd2897

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Huang JG, Leshuk T, Gu FX (2011) Emerging nanomaterials for targeting subcellular organelles. Nano Today 6(5):478–492. https://doi.org/10.1016/j.nantod.2011.08.002

    CAS  Article  Google Scholar 

  5. 5.

    Kang JW, So PTC, Dasari RR, Lim D-K (2015) High resolution live cell Raman imaging using subcellular organelle-targeting SERS—sensitive gold nanoparticles with highly narrow intra-nanogap. Nano Lett 15(3):1766–1772. https://doi.org/10.1021/nl504444w

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Ma X, Zhang LR, Wang X, Xue SJH, Wu Y (2012) Single walled carbon nanotubes alter cytochrome c electron transfer and modulate mitochondrial function. ACS Nano 6(12):10486–10496. https://doi.org/10.1021/nn302457v

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Wang P, Wang X, Wang L, Hou X, Liu W, Chen C (2015) Interaction of gold nanoparticles with proteins and cells. Sci Technol Adv Mater 16(3):034610–034625. https://doi.org/10.1088/1468-6996/16/3/034610

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Patra HK, Banerjee S, Chaudhuri U, Lahiri P, Dasgupta AK (2007) Cell selective response to gold nanoparticles. J Nano 3:111–119

    CAS  Google Scholar 

  9. 9.

    Coradeghini R, Gioria S, García CP, Nativo P, Franchini F, Gilliland D, Ponti J, Rossi F (2013) Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts. Toxicol Lett 217(3):205–216. https://doi.org/10.1016/j.toxlet.2012.11.022

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Uboldi C, Bonacchi D, Lorenzi G, Hermanns MI, Pohl C, Baldi G, Unger RE, Kirkpatrick CJ (2009) Gold nanoparticle induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH44I. Part Fibre Toxicol 1(1):6–18. https://doi.org/10.1186/1743-8977-6-18

    CAS  Article  Google Scholar 

  11. 11.

    Lévy R, Shaheen U, Cesbron Y, Sée V (2010) Gold nanoparticles delivery in mammalian cells: a critical review. Nano Rev 1:3402–3420

    Article  Google Scholar 

  12. 12.

    Zhang Y, Xu D, Li W, Yu J, Chen Y (2012) Effect of size, shape, and surface modification on cytotoxicity of gold nanoparticles to human HEp-2 and canine MDCK cells. J Nanomater 1:375496–375497. https://doi.org/10.1155/2012/375496

    CAS  Article  Google Scholar 

  13. 13.

    Barizuddin S, Bok S, Gangopadhyay S (2016) Plasmonic sensors for disease detection—a review. J Nanomed Nanotechnol 7(3):1000373. https://doi.org/10.4172/2157-7439.1000373

    CAS  Article  Google Scholar 

  14. 14.

    Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6(4):662–668. https://doi.org/10.1021/nl052396o

    CAS  Article  Google Scholar 

  15. 15.

    Zhao J, Zhang X, Yonzon CR, Haes AJ, Van Duyne RP (2006) Localized surface plasmon resonance biosensors. Nanomedicine 1:2.219

    Article  Google Scholar 

  16. 16.

    Unser S, Bruzas I, He J, Sagle L (2015) Localized surface plasmon resonance biosensing: current challenges and approaches. Sensors 15(7):15684–15716. https://doi.org/10.3390/s150715684

    Article  PubMed  Google Scholar 

  17. 17.

    Lee YE, Smith R, Kopelman R (2009) Nanoparticle PEBBLE sensors in live cells and in vivo. Annu Rev Anal Chem 2:57–56

    Article  Google Scholar 

  18. 18.

    Huang X, El-Sayed MA (2010) Gold nanoparticles: optical properties and implementations in cancer diagnosis and photothermal therapy. J Adv Res 1(1):13–28. https://doi.org/10.1016/j.jare.2010.02.002

    Article  Google Scholar 

  19. 19.

    Beaudet D, Badilescu S, Kuruvinashetti K, Sohrabi Kashani A, Jaunky D, Ouellette S, Piekny A, Packirisamy M (2017) Comparative study on cellular entry of incinerated ancient gold particles (Swarna Bhasma) and chemically synthesized gold particles. Nat Sci Rep 7(1):10678. https://doi.org/10.1038/s41598-017-10872-3

    Article  Google Scholar 

  20. 20.

    Yang C, Uertz J, Yohan D, Chithrani BD (2014) Peptide modified gold nanoparticles for improved cellular uptake, nuclear transport and intracellular retention. Nano 6:12026–12033

    CAS  Google Scholar 

  21. 21.

    Klingberg H, Oddershede LB, Loeschner K, Larsen EH, Lofta S, Møller P (2015) Uptake of gold nanoparticles in primary human endothelial cells. Toxicol Res 4(3):655–666. https://doi.org/10.1039/c4tx00061g

    CAS  Article  Google Scholar 

  22. 22.

    Murphy CJ, Gole AM, Stone JW, Sisco PN, Alkilany AM, Goldsmith EC, Baxter SC (2008) Gold nanoparticles in biology: beyond toxicity to cellular imaging. Acc Chem Res 41(12):1721–1730. https://doi.org/10.1021/ar800035u

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Vetten MA, Tlotleng N, Tanner Rascher D, Skepu A, Keter FK, Boodhia K, Koekemoer LA, Andraos C, Tshikhudo R, Gulumian M (2013) Label-free in vitro toxicity and uptake assessment of citrate stabilized gold nanoparticles in three cell lines. Part Fibre Toxicol 10(1):50. https://doi.org/10.1186/1743-8977-10-50

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Vishnupriya S, Chaudhari K, Jagannathan R, Pradeep T (2013) Single cell investigations of silver nanoparticle-bacteria interactions. Part Part Syst Charact 30(12):1056–1062. https://doi.org/10.1002/ppsc.201300165

    CAS  Article  Google Scholar 

  25. 25.

    Gölzhäuser A, Tanguay RL, Liang X-J, Parak WJ (2017) Colloidal gold nanoparticles induce changes in cellular and subcellular morphology. ACS Nano 11:7807–7820

    Article  Google Scholar 

  26. 26.

    Tong Q, Xue Y, Zhang L (2013) Progress in hyperspectral remote sensing science and technology in China over the past three decades. IEEE J-STARS 7(1):2267204

    Google Scholar 

  27. 27.

    Ben-Dor E, Schläpfer D, Plaza AJ, Malthus T (2013) Hyperspectral remote sensing. Wiley – VCH Verlag GmbH & Co. KGaA, pp 413–455

  28. 28.

    Roth GA, Tahiliani S, Neu-Baker NM, Brenner SA (2015) Hyperspectral microscopy as an analytical tool for nanomaterials. Nanomed Nanobiotechnol 7(4):565–579. https://doi.org/10.1002/wnan.1330

    CAS  Article  Google Scholar 

  29. 29.

    Turkevich J, Cooper Stevenson P, Hillier J (1951) A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 11:55–75. https://doi.org/10.1039/df9511100055

    Article  Google Scholar 

  30. 30.

    Kimling J, Maier M, Okenve B, Kotaidis V, Ballot H, Plech A (2006) Turkevich method for gold nanoparticle synthesis revisited. J Phys Chem 110(32):15700–15707. https://doi.org/10.1021/jp061667w

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The authors are grateful for the help and support from Dr. Stewart Mills (CytoViva, Auburn, Alabama, USA) in hyperspectral imaging.

Funding

Financial support from Natural Sciences and Engineering Research Council of Canada (NSERC) grant of A. Piekny and NSERC, Concordia Research Chair and Fonds de recherché Nature et technologies (FRQNT) grants of M. Packirisamy are also acknowledged.

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Correspondence to Muthukumaran Packirisamy.

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Kuruvinashetti, K., Kashani, A.S., Badilescu, S. et al. Intracellular Localized Surface Plasmonic Sensing for Subcellular Diagnosis. Plasmonics 13, 1639–1648 (2018). https://doi.org/10.1007/s11468-017-0673-3

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Keywords

  • Intracellular plasmonics
  • Hyperspectral microscopy
  • Gold nanoparticles