Skip to main content
SpringerLink
Log in

Toxicity and biodistribution of nanodiamond coupled with calcein

  • Materials for life sciences
  • Published:
Journal of Materials Science Aims and scope Submit manuscript

Abstract

Due to its small particle size, high specific surface area, functional capability and long-term stable fluorescence, nanodiamond (ND) has been widely used in biomedical applications including fluorescent probes, drug delivery and biological imaging. Nevertheless, the metabolism of ND and its derivatives is not yet well understood for diverse biomedical applications. In this study, to evaluate the cytotoxicity and biodistribution of the ND derivative, pure ND was functionalized with ethylenediamine (EDA) as a linker (ND-EDA) and then covalently labeled with an organic fluorescent dye called calcein. The modified ND is referred to as ND-EDA-calcein. Even at the maximum dose of 0.1 mg·mL−1, the in vitro results for ND-EDA-calcein against HepG2 and LO2 cell lines showed negligible cytotoxicity, which was in line with the in vivo observations. In addition, it was found that following an intraperitoneal injection, ND-EDA-calcein could be accumulated mostly in the liver and kidney of the mice but not in the spleen. It is interesting to note that after 5 days following intraperitoneal injection, mice can totally metabolize the elimination of ND-EDA-calcein outside of their bodies. Therefore, our findings suggested that NDs can be considered for various nanomedicine applications including drug delivery and biomarkers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

Data availability

The data presented in this study are available on request from the corresponding author.

Code availability

The data presented in this study are available on request from the corresponding author.

References

  1. Chang YR, Lee HY, Chen K et al (2008) Mass production and dynamic imaging of fluorescent nanodiamonds. Nat Nanotechnol 3:284–288. https://doi.org/10.1038/nnano.2008.99

    Article  CAS  Google Scholar 

  2. Haziza S, Mohan N, Loe-Mie Y et al (2017) Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors. Nat Nanotechnol 12:322–328. https://doi.org/10.1038/nnano.2016.260

    Article  CAS  Google Scholar 

  3. Zhang QW, Mochalin VN, Neitzel I et al (2012) Mechanical properties and biomineralization of multifunctional nanodiamond-PLLA composites for bone tissue engineering. Biomaterials 33:5067–5075. https://doi.org/10.1016/j.biomaterials.2012.03.063

    Article  CAS  Google Scholar 

  4. McGuinness LP, Yan Y, Stacey A et al (2011) Quantum measurement and orientation tracking of fluorescent nanodiamonds inside living cells. Nat Nanotechnol 6:358–363. https://doi.org/10.1038/nnano.2011.64

    Article  CAS  Google Scholar 

  5. Nie L, Nusantara AC, Damle VG et al (2021) Quantum monitoring of cellular metabolic activities in single mitochondria. Sci Adv 7:8. https://doi.org/10.1126/sciadv.abf0573

    Article  CAS  Google Scholar 

  6. Yukawa H, Fujiwara M, Kobayashi K et al (2020) A quantum thermometric sensing and analysis system using fluorescent nanodiamonds for the evaluation of living stem cell functions according to intracellular temperature. Nanoscale Adv 2:1859–1868. https://doi.org/10.1039/d0na00146e

    Article  CAS  Google Scholar 

  7. Uthappa UT, Arvind OR, Sriram G, Losic D, Ho Young J, Kigga M, Kurkuri MD (2020) Nanodiamonds and their surface modification strategies for drug delivery applications. J Drug Deliv Sci Technol 60:16. https://doi.org/10.1016/j.jddst.2020.101993

    Article  CAS  Google Scholar 

  8. Vaijayanthimala V, Lee DK, Kim SV et al (2015) Nanodiamond-mediated drug delivery and imaging: challenges and opportunities. Expert Opin Drug Deliv 12:735–749. https://doi.org/10.1517/17425247.2015.992412

    Article  CAS  Google Scholar 

  9. Fox K, Tran PA, Lau DWM, Ohshima T, Greentree AD, Gibson BC (2016) Nanodiamond-polycaprolactone composite: a new material for tissue engineering with sub-dermal imaging capabilities. Mater Lett 185:185–188. https://doi.org/10.1016/j.matlet.2016.08.140

    Article  CAS  Google Scholar 

  10. Mochalin VN, Shenderova O, Ho D, Gogotsi Y (2012) The properties and applications of nanodiamonds. Nat Nanotechnol 7:11–23. https://doi.org/10.1038/nnano.2011.209

    Article  CAS  Google Scholar 

  11. Yan JL, Estevez MC, Smith JE, Wang KM, He XX, Wang L, Tan WH (2007) Dye-doped nanoparticles for bioanalysis. Nano Today 2:44–50. https://doi.org/10.1016/s1748-0132(07)70086-5

    Article  Google Scholar 

  12. Hong C, Song D, Lee DK et al (2017) Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen-nanodiamond hydrogel. Proc Natl Acad Sci USA 114:E7218–E7225. https://doi.org/10.1073/pnas.1704027114

    Article  CAS  Google Scholar 

  13. Pacelli S, Maloney R, Chakravarti AR et al (2017) Controlling adult stem cell behavior using nanodiamond-reinforced hydrogel: implication in bone regeneration therapy. Sci Rep 7:15. https://doi.org/10.1038/s41598-017-06028-y

    Article  CAS  Google Scholar 

  14. Chauhan S, Jain N, Nagaich U (2020) Nanodiamonds with powerful ability for drug delivery and biomedical applications: recent updates on in vivo study and patents. J Pharm Anal 10:1–12. https://doi.org/10.1016/j.jpha.2019.09.003

    Article  Google Scholar 

  15. Moore L, Grobarova V, Shen H et al (2014) Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds. Nanoscale 6:11712–11721. https://doi.org/10.1039/c4nr02570a

    Article  CAS  Google Scholar 

  16. Marcon L, Riquet F, Vicogne D, Szunerits S, Bodart JF, Boukherroub R (2010) Cellular and in vivo toxicity of functionalized nanodiamond in Xenopus embryos. J Mater Chem 20:8064–8069. https://doi.org/10.1039/c0jm01570a

    Article  CAS  Google Scholar 

  17. Puzyr AP, Neshumayev DA, Tarskikh SV, Makarskaya GV, Dolmatov VY, Bondar VS (2004) Destruction of human blood cells in interaction with detonation nanodiamonds in experiments in vitro. Diam Relat Mater 13:2020–2023. https://doi.org/10.1016/j.diamond.2004.06.003

    Article  CAS  Google Scholar 

  18. Schrand AM, Huang HJ, Carlson C, Schlager JJ, Osawa E, Hussain SM, Dai LM (2007) Are diamond nanoparticles cytotoxic? J Phys Chem B 111:2–7. https://doi.org/10.1021/jp066387v

    Article  CAS  Google Scholar 

  19. Yu SJ, Kang MW, Chang HC, Chen KM, Yu YC (2005) Bright fluorescent nanodiamonds: no photobleaching and low cytotoxicity. J Am Chem Soc 127:17604–17605. https://doi.org/10.1021/ja0567081

    Article  CAS  Google Scholar 

  20. Lai L, Barnard AS (2015) Functionalized nanodiamonds for biological and medical applications. J Nanosci Nanotechnol 15:989–999. https://doi.org/10.1166/jnn.2015.9735

    Article  CAS  Google Scholar 

  21. Tjo K, Varamini P (2022) Nanodiamonds and their potential applications in breast cancer therapy: a narrative review. Drug Deliv Transl Res 12:1017–1028. https://doi.org/10.1007/s13346-021-00996-5

    Article  CAS  Google Scholar 

  22. Wu YZ, Ermakova A, Liu WN et al (2015) Programmable biopolymers for advancing biomedical applications of fluorescent nanodiamonds. Adv Funct Mater 25:6576–6585. https://doi.org/10.1002/adfm.201502704

    Article  CAS  Google Scholar 

  23. Zhang T, Neumann A, Lindlau J et al (2015) DNA-based self-assembly of fluorescent nanodiamonds. J Am Chem Soc 137:9776–9779. https://doi.org/10.1021/jacs.5b04857

    Article  CAS  Google Scholar 

  24. Inzhevatkin E, Baron A, Maksimov N, Volkova M, Puzyr A, Ronzhin N, Bondar V (2019) Biodistribution of nanodiamonds in the body of mice using EPR spectrometry. IET Sci Meas Technol 13:984–988. https://doi.org/10.1049/iet-smt.2018.5594

    Article  Google Scholar 

  25. Hong SP, Ha SW, Lee SW (2018) Atmospheric-pressure chemical purification of detonation-synthesized nanodiamond by using perchloric acid: intensive parametric study to control sp(3)/sp(2)carbon ratio. Diam Relat Mater 81:27–32. https://doi.org/10.1016/j.diamond.2017.11.006

    Article  CAS  Google Scholar 

  26. Cao Y, Fang MX, Cai XJ, Shi SR, Liu C (2020) Preparation method for monodispersed aminated nano-diamond colloid solution, secondary dispersion process therefor, and application thereof in cell labeling. In: Chemical indexing equivalent to 172:262083 (CN), p 31

Download references

Acknowledgements

This research was supported by the Fundamental Research Funds for the Central Universities and Hubei Provincial Department of Education (Q20183005).

Author information

Author notes

  1. Xuelin Wu, Jiaying Qu and Laizaiti Asibaike have equally contributed to this work.

Authors and Affiliations

  1. Key Laboratory of Pesticide & Chemical Biology (Ministry of Education), College of Chemistry, Central China Normal University, Wuhan, 430079, People’s Republic of China

    Xuelin Wu, Jiaying Qu, Laizaiti Asibaike, Yuyang Sun, Jean Felix Mukerabigwi, Xueying Huang & Yu Cao

  2. Hubei Key Laboratory of Purification and Application of Plant Anti-Cancer Active Ingredients, Hubei University of Education, Wuhan, 430205, People’s Republic of China

    Jiaying Qu & Didi Chen

  3. Department of Chemistry, College of Science and Technology, University of Rwanda, Po. Box: 3900, Kigali, Rwanda

    Jean Felix Mukerabigwi

Authors
  1. Xuelin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiaying Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laizaiti Asibaike
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuyang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Didi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean Felix Mukerabigwi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xueying Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yu Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XW and YC conceptualized the study; XW contributed to methodology, investigation, resources and writing—original draft preparation; JQ assisted with the software; XW, YC and JQ carried out validation; YC and LA performed formal analysis; XW and YS curated the data; YC took part in writing—review and editing, project administration and funding acquisition; XH participated in visualization; and DC and JM were involved in supervision. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Didi Chen or Yu Cao.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This study has been approved by the Ethics Committee of Central China Normal University, Wuhan, China.

Additional information

Handling Editor: Dale Huber.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 153 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, X., Qu, J., Asibaike, L. et al. Toxicity and biodistribution of nanodiamond coupled with calcein. J Mater Sci 58, 12764–12774 (2023). https://doi.org/10.1007/s10853-023-08808-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10853-023-08808-6

Search

Navigation