Skip to main content
SpringerLink
Log in

A Novel Fluorescent Quantum Dot Probe for the Rapid Diagnostic High Contrast Imaging of Tumor in Mice

  • ORIGINAL ARTICLE
  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

A simple probe - antibody conjugated silica over coated cadmium selenide quantum dots (QD-Ab probe) for efficient and rapid diagnostic in vivo imaging of tumors is developed. Compared to unconjugated quantum dots (QD), these probes underwent efficient cellular internalization and tumor targeting behavior, retaining bright emission under in vivo cancer models. Silica over coated cadmium selenide quantum dots were conjugated with Epidermal growth factor receptor (EGFR) monoclonal antibody to detect the over expression of EGFR in cancer models. The in vitro cellular internalization efficiency of QD and QD-Ab probe in cultured stem cells (RADMSCs) and cancer cells (HeLa) were assessed by ICP-OES and cLSM. Results demonstrated a greater internalization efficiency of CdSe-Silica QD-Ab probe than CdSe-Silica QDs. For in vivo imaging solid tumor bearing mice was subjected to tail vein injection of QD and QD-Ab probe. After the specific time interval of injection, mice were anesthetized and subjected into Xenogen IVIS®200 imaging system, followed by ex vivo imaging. Subsequently, ultrathin sections of tumor were imaged by using cLSM. Both in vivo and ex vivo imaging results confirmed the tumor-targeted imaging efficiency of QD-Ab probes compared to unconjugated QDs.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Katz E, Willner I (2004) Integrated nanoparticle-biomolecule hybrid systems: synthesis, properties, and applications. Angew Chem Int Ed 43:6042–108

    Article  CAS  Google Scholar 

  2. Cai WB, Chen XY (2007) Nanoplatforms for targeted molecular imaging in living subjects. Small 3:1840–1854

    Article  CAS  PubMed  Google Scholar 

  3. Smith AM, Nie S (2004) Chemical analysis and cellular imaging with quantum dots. Analyst 129:672–677

    Article  CAS  PubMed  Google Scholar 

  4. Alivisatos AP, Gu WW, Larabell C (2005) Quantum dots as cellular probes. Annu Rev Biomed Eng 7:55–76

    Article  CAS  PubMed  Google Scholar 

  5. Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Vibin M, Vinayakan R, John A, Raji V, Rejiya CS, Abraham A (2011) Fluorescence imaging of stem cells, cancer cells and semi-thin sections of tissues using silica coated CdSe quantum dots. J Fluoresc 21:1365–1370

    Article  CAS  PubMed  Google Scholar 

  7. Yang L, Mao H, Wang YA, Cao Z, Peng X, Wang X, Duan H, Ni C, Yuan Q, Adams G, Smith MQ, Wood WC, Gao X, Nie S (2009) Single chain epidermal growth factor receptor antibody conjugated nanoparticles for in vivo tumor targeting and imaging. Small 5:235–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yong KT, Roy I, Ding H, Bergey EJ, Prasad PN (2009) Biocompatible near-infrared quantum dots as ultrasensitive probes for long-term in vivo imaging applications. Small 5:1997–2004

    Article  CAS  PubMed  Google Scholar 

  9. Derfus AM, Chan WCW, Bhatia SN (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4:11–18

    Article  CAS  Google Scholar 

  10. Kirchner C, Liedl T, Kudera S, Pellegrino T, Munoz Javier A, Gaub HE, Stölzle S, Fertig N, Parak WJ (2005) Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett 5:331–338

    Article  CAS  PubMed  Google Scholar 

  11. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, Bawendi MG, Frangioni JV (2007) Renal clearance of quantum dots. Nat Biotechnol 25:1165–1170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pellegrino T, Kudera S, Liedl T, Javier AM, Manna L, Parak WJ (2005) On the development of colloidal nanoparticles towards multifunctional structures and their possible use for biological applications. Small 1:48–63

    Article  CAS  PubMed  Google Scholar 

  13. Selvan ST, Patra PK, Ang CY, Ying JY (2007) Synthesis of silica coated semiconductor and magnetic quantum dots and their use in the imaging of live cells. Angew Chem Int Ed 46:2448–2452

    Article  CAS  Google Scholar 

  14. Bakalova R, Zhelev Z, Aoki I, Ohba H, Imai Y, Kanno I (2006) Silica-shelled single quantum dot micelles as imaging probes with dual or multimodality. Anal Chem 78:5925–5932

    Article  CAS  PubMed  Google Scholar 

  15. Chen F, Gerion D (2004) Fluorescent CdSe/ZnS nanocrystalpeptide conjugates for long-term, nontoxic imaging and nuclear targeting in living cells. Nano Lett 4:1827–1832

    Article  CAS  Google Scholar 

  16. Han R, Yu M, Zheng Q, Wang L, Hong Y, Sha Y (2009) A facile synthesis of small-sized, highly photoluminescent, and monodisperse CdSeS QD/SiO2 for live cell imaging. Langmuir 25:12250–12255

    Article  CAS  PubMed  Google Scholar 

  17. Stroh M, Zimmer JP, Duda DG, Levchenko TS, Cohen KS, Brown EB, Scadden DT, Torchilin VP, Bawendi MG, Fukumura D, Jain RK (2005) Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat Med 11:678–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Vibin M, Vinayakan R, John A, Raji V, Rejiya CS, Abraham A (2011) Cellular uptake and subcellular localization of highly luminescent silica coated CdSe quantum dots – In vitro and in vivo. J Colloid Interface Sci 357:366–371

    Article  CAS  PubMed  Google Scholar 

  19. Yong KT, Ding H, Roy I, Law WC, Bergey EJ, Maitra A, Prasad PN (2009) Imaging pancreatic cancer using bioconjugated InP quantum dots. ACS Nano 3:502–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Law WC, Yong KT, Roy I, Ding H, Hu R, Zhao W, Prasad PN (2009) Aqueous-phase synthesis of highly luminescent CdTe/ZnTe core/shell quantum dots optimized for targeted bioimaging. Small 5:1302–1310

    Article  CAS  PubMed  Google Scholar 

  21. Vibin M, Vinayakan R, John A, Raji V, Rejiya CS, Vinesh NS, Abraham A (2011) Cytotoxicity and fluorescence studies of silica coated CdSe quantum dots for bioimaging applications. J Nanopart Res 13:2587–2596

    Article  CAS  Google Scholar 

  22. Chen C, Peng J, Xia H, Yang G, Wu Q, Zeng CL, Zhang Z, Pang D, Li Y (2009) Quantum dots-based immunofluorescence technology for the quantitative determination of HER2 expression in breast cancer. Biomaterials 30:2912–2918

    Article  CAS  PubMed  Google Scholar 

  23. Chiu SJ, Liu S, Perrotti D, Marcucci G, Lee RJ (2006) Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes. J Control Release 112:199–207

    Article  CAS  PubMed  Google Scholar 

  24. Lee RJ, Low PS (1994) Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis. J Biol Chem 269:3198–3204

    CAS  PubMed  Google Scholar 

  25. Li Z, Huang P, Zhang X, Lin J, Yang S, Liu B, Gao F, Xi P, Ren Q, Cui D (2010) RGD-conjugated dendrimer-modified gold nanorods for in vivo tumor targeting and photothermal therapy. Mol Pharm 7:94–104

    Article  CAS  PubMed  Google Scholar 

  26. Chrastina A, Valadon P, Massey KA, Schnitzer JE (2010) Lung vascular targeting using antibody to aminopeptidase P: CT-SPECT imaging, biodistribution and pharmacokinetic analysis. J Vasc Res 47:531–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tan WB, Jiang S, Zhang Y (2007) Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. Biomaterials 28:1565–1571

    Article  CAS  PubMed  Google Scholar 

  28. Peng XA, Peng XG (2001) Formation of high-quality CdTe, CdSe, and CdS nanocrystals using CdO as precursor. J Am Chem Soc 123:183–184

    Article  CAS  PubMed  Google Scholar 

  29. Vinayakan R, Shanmugapriya T, Nair PV, Ramamurthy P, Thomas KG (2007) An approach for optimizing the shell thickness of core-shell quantum dots using photoinduced charge transfer. J Phys Chem C 111:10146–10149

    Article  CAS  Google Scholar 

  30. Vibin M, Vinayakan R, John A, Raji V, Rejiya CS, Abraham A (2011) Biokinetics and in vivo distribution behaviours of silica coated cadmium selenide quantum dots. Biol Trace Elem Res 142:213–222

    Article  CAS  PubMed  Google Scholar 

  31. Rejiya CS, Kumar J, Raji V, Vibin M, Abraham A (2012) Laser immunotherapy with gold nanorods causes selective killing of tumour cells. Pharmacol Res 65:261–269

    Article  CAS  Google Scholar 

  32. Siveen KS, Kuttan G (2011) Immunomodulatory and antitumor activity of Aerva lanata ethanolic extract. Immunopharmacol Immunotoxicol 33:423–432

    Article  CAS  PubMed  Google Scholar 

  33. Lim YT, Kim S, Nakayama A, Stott NE, Bawendi MG, Frangioni JV (2003) Selection of quantum dot wavelengths for biomedical assays and imaging. Mol Imaging 2:50–64

    Article  CAS  PubMed  Google Scholar 

  34. Yang PH, Sun XS, Chiu JF, Sun HZ, He QY (2005) Transferrin-mediated gold nanoparticle cellular uptake. Bioconjug Chem 16:494–496

    Article  CAS  PubMed  Google Scholar 

  35. Gu W, Pellegrino T, Parak WJ, Boudreau R, Le Gros MA, Alivisatos AP, Larabell CA (2007) Measuring cell motility using quantum dot probe. Methods Mol Bio 374:125–132

    Google Scholar 

  36. Yang K, Zhang FJ, Tang H, Zhao C, Cao YA, Lv XQ, Chen D, Li YD (2011) In-vivo imaging of oral squamous cell carcinoma by EGFR monoclonal antibody conjugated near-infrared quantum dots in mice. Int J Nanomedicine 6:1739–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lee J, Choi Y, Kim K, Hong S, Park HY, Lee T, Cheon GJ, Song R (2010) Characterization and cancer cell specific binding properties of anti-EGFR antibody conjugated quantum dots. Bioconjug Chem 21:940–946

    Article  CAS  PubMed  Google Scholar 

  38. Alivisatos AP (1996) Semiconductor clusters, nanocrystals, and quantum dots. Science 271:933–937

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Department of Biotechnology, Ministry of Science and Technology, Govt. of India, New Delhi (Order No. BT/PR9904/NNT/28/63/2007). We thank to Prof. K. George Thomas, Dean, IISER, Thiruvananthapuram, India for providing nanomaterials; Dr. Jayasree, Dr. T. V. Anilkumar and Dr. H. K. Varma, SCTIMST, India for providing in vivo imaging, cLSM and ICP-OES facility. We thank Dr. Ommathanu Perumal, Prof & Head, Department of Pharmaceutical Sciences, South Dakota State University, USA for fruitful discussion. M.V. thank UGC, Govt. of India for Raman Indo-US Post-Doctoral Fellowship.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthapuram, 695581, Kerala, India

    M. Vibin & Annie Abraham

  2. Department of Biochemistry, St. Albert’s College, Mahatma Gandhi University, Ernakulam, Kochi, 682018, Kerala, India

    M. Vibin

  3. Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD, 57007, USA

    M. Vibin

  4. Department of Chemistry, SVR NSS College Vazhoor, Mahatma Gandhi University, Kottayam, 686505, Kerala, India

    R. Vinayakan

  5. TEM Laboratory, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Biomedical Technology Wing, Thiruvananthapuram, 695012, Kerala, India

    F. B. Fernandez & Annie John

Authors
  1. M. Vibin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Vinayakan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. B. Fernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Annie John
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annie Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Annie Abraham.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 165 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vibin, M., Vinayakan, R., Fernandez, F.B. et al. A Novel Fluorescent Quantum Dot Probe for the Rapid Diagnostic High Contrast Imaging of Tumor in Mice. J Fluoresc 27, 669–677 (2017). https://doi.org/10.1007/s10895-016-1996-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10895-016-1996-8

Keywords

Search

Navigation