Skip to main content

Advertisement

SpringerLink
Log in

Anti-HER2 VHH Targeted Magnetoliposome for Intelligent Magnetic Resonance Imaging of Breast Cancer Cells

  • Published:
Cellular and Molecular Bioengineering Aims and scope Submit manuscript

Abstract

The combination of liposomes with magnetic nanoparticles, because of their strong effect on T2 relaxation can open new ways in the innovative cancer therapy and diagnosis. In order to design an intelligent contrast agent in MRI, we chose anti-HER2 nanobody the smallest fully functional antigen-binding fragments evolved from the variable domain, the VHH, of a camel heavy chain-only antibody. These targeted magnetoliposomes bind to the HER2 antigen which is highly expressed on breast and ovarian cancer cells so reducing the side effects as well as increasing image contrast and effectiveness. Cellular iron uptake analysis and in vitro MRI of HER2 positive cells incubated with targeted nanoparticles show specific cell targeting. In vitro MRI shows even at the lowest density (200 Cells/μl), dark spots corresponding to labeled cells which were still detectable. These results suggest that this new type of nanoparticles could be effective antigen-targeted contrast agents for molecular imaging.

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.

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

Similar content being viewed by others

References

  1. Bonnet, C. S., Tóth É. MRI contrast agents. In: Ligand Design in Medicinal Inorganic Chemistry, 2014, pp. 321–354.

  2. Clift, M. J., B. Rothen-Rutishauser, D. M. Brown, R. Duffin, K. Donaldson, L. Proudfoot, et al. The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line. Toxicol. Appl. Pharmacol. 232(3):418–427, 2008.

    Article  Google Scholar 

  3. De Cuyper, M., S. J. Soenen, K. Coenegrachts, and L. T. Beek. Surface functionalization of magnetoliposomes in view of improving iron oxide-based magnetic resonance imaging contrast agents: anchoring of gadolinium ions to a lipophilic chelate. Anal. Biochem. 367(2):266–273, 2007.

    Article  Google Scholar 

  4. De Meyer, T., S. Muyldermans, and A. Depicker. Nanobody-based products as research and diagnostic tools. Trends Biotechnol. 32(5):263–270, 2014.

    Article  Google Scholar 

  5. Faria, M., M. Cruz, M. Gonçalves, A. Carvalho, G. Feio, and M. Martins. Synthesis and characterization of magnetoliposomes for MRI contrast enhancement. Int. J. Pharm. 446(1):183–190, 2013.

    Article  Google Scholar 

  6. Frascione, D., C. Diwoky, G. Almer, P. Opriessnig, C. Vonach, K. Gradauer, et al. Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes. Int. J. Nanomed. 7:2349, 2012.

    Google Scholar 

  7. Jamnani, F. R., F. Rahbarizadeh, M. A. Shokrgozar, D. Ahmadvand, F. Mahboudi, and Z. Sharifzadeh. Targeting high affinity and epitope-distinct oligoclonal nanobodies to HER2 over-expressing tumor cells. Exp. Cell Res. 318(10):1112–1124, 2012.

    Article  Google Scholar 

  8. Jamnani, F. R., F. Rahbarizadeh, M. A. Shokrgozar, F. Mahboudi, D. Ahmadvand, Z. Sharifzadeh, et al. T cells expressing VHH-directed oligoclonal chimeric HER2 antigen receptors: towards tumor-directed oligoclonal T cell therapy. Biochim. Biophys. Acta (BBA)-Gen. Subj. 1840(1):378–386, 2014.

    Article  Google Scholar 

  9. Khaleghi, S., F. Rahbarizadeh, D. Ahmadvand, M. Malek, and H. R. Madaah Hosseini. The effect of superparamagnetic iron oxide nanoparticles surface engineering on relaxivity of magnetoliposome. Contrast Media Mol. Imaging 11:340, 2016.

    Article  Google Scholar 

  10. Lima-Tenório, M. K., E. A. G. Pineda, N. M. Ahmad, H. Fessi, and A. Elaissari. Magnetic nanoparticles: in vivo cancer diagnosis and therapy. Int. J. Pharm. 493(1):313–327, 2015.

    Article  Google Scholar 

  11. Lu, R.-M., Y.-L. Chang, M.-S. Chen, and H.-C. Wu. Single chain anti-c-Met antibody conjugated nanoparticles for in vivo tumor-targeted imaging and drug delivery. Biomaterials 32(12):3265–3274, 2011.

    Article  Google Scholar 

  12. Moghimi, S. M., F. Rahbarizadeh, D. Ahmadvand, and L. Parhamifar. Heavy chain only antibodies: a new paradigm in personalized HER2+ breast cancer therapy. BioImpacts: BI 3(1):1, 2013.

    Google Scholar 

  13. Oliveira, S., R. M. Schiffelers, J. van der Veeken, R. van der Meel, R. Vongpromek, P. M. V. B. en Henegouwen, et al. Downregulation of EGFR by a novel multivalent nanobody-liposome platform. J. Control. Release 145(2):165–175, 2010.

    Article  Google Scholar 

  14. Reynolds, J. G., E. Geretti, B. S. Hendriks, H. Lee, S. C. Leonard, S. G. Klinz, et al. HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity. Toxicol. Appl. Pharmacol. 262(1):1–10, 2012.

    Article  Google Scholar 

  15. Rotman, M., M. M. Welling, A. Bunschoten, M. E. de Backer, J. Rip, R. J. Nabuurs, et al. Enhanced glutathione PEGylated liposomal brain delivery of an anti-amyloid single domain antibody fragment in a mouse model for Alzheimer’s disease. J. Control. Release 203:40–50, 2015.

    Article  Google Scholar 

  16. Sabaté, R., R. Barnadas-Rodríguez, J. Callejas-Fernández, R. Hidalgo-Álvarez, and J. Estelrich. Preparation and characterization of extruded magnetoliposomes. Int. J. Pharm. 347(1):156–162, 2008.

    Article  Google Scholar 

  17. Sadeqzadeh, E., F. Rahbarizadeh, D. Ahmadvand, M. J. Rasaee, L. Parhamifar, and S. M. Moghimi. Combined MUC1-specific nanobody-tagged PEG-polyethylenimine polyplex targeting and transcriptional targeting of tBid transgene for directed killing of MUC1 over-expressing tumour cells. J. Control. Release 156(1):85–91, 2011.

    Article  Google Scholar 

  18. Sharifzadeh, Z., F. Rahbarizadeh, M. A. Shokrgozar, D. Ahmadvand, F. Mahboudi, F. R. Jamnani, et al. Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents. Cancer Lett. 334(2):237–244, 2013.

    Article  Google Scholar 

  19. Shinkai, M., M. Suzuki, S. Iijima, and T. Kobayashi. Antibody-conjugated magnetoliposomes for targeting cancer cells and their application in hyperthermia. Biotechnol. Appl. Biochem. 21(2):125–137, 1995.

    Article  Google Scholar 

  20. Singh, A., and S. K. Sahoo. Magnetic nanoparticles: a novel platform for cancer theranostics. Drug Discov. Today 19(4):474–481, 2014.

    Article  Google Scholar 

  21. Soenen, S. J., J. Baert, and M. De Cuyper. Optimal conditions for labelling of 3T3 fibroblasts with magnetoliposomes without affecting cellular viability. Chembiochem 8(17):2067–2077, 2007.

    Article  Google Scholar 

  22. Soenen, S. J., M. De Cuyper, S. C. De Smedt, and K. Braeckmans. Investigating the toxic effects of iron oxide nanoparticles. Methods Enzymol. 509:195–224, 2012.

    Article  Google Scholar 

  23. Soenen, S. J., S. F. De Meyer, T. Dresselaers, G. V. Velde, I. M. Pareyn, K. Braeckmans, et al. MRI assessment of blood outgrowth endothelial cell homing using cationic magnetoliposomes. Biomaterials 32(17):4140–4150, 2011.

    Article  Google Scholar 

  24. Soenen, S. J., G. V. Velde, A. Ketkar-Atre, U. Himmelreich, and M. De Cuyper. Magnetoliposomes as magnetic resonance imaging contrast agents. Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol. 3(2):197–211, 2011.

    Google Scholar 

  25. Steinhauser, I., B. Spänkuch, K. Strebhardt, and K. Langer. Trastuzumab-modified nanoparticles: optimisation of preparation and uptake in cancer cells. Biomaterials 27(28):4975–4983, 2006.

    Article  Google Scholar 

  26. Van de Broek, B., N. Devoogdt, A. D’Hollander, H.-L. Gijs, K. Jans, L. Lagae, et al. Specific cell targeting with nanobody conjugated branched gold nanoparticles for photothermal therapy. ACS Nano 5(6):4319–4328, 2011.

    Article  Google Scholar 

  27. Wray, W., T. Boulikas, V. P. Wray, and R. Hancock. Silver staining of proteins in polyacrylamide gels. Anal. Biochem. 118(1):197–203, 1981.

    Article  Google Scholar 

  28. Yigit, M. V., A. Moore, and Z. Medarova. Magnetic nanoparticles for cancer diagnosis and therapy. Pharm. Res. 29(5):1180–1188, 2012.

    Article  Google Scholar 

Download references

Conflict of Interest

The authors (Sepideh Khaleghi, Fatemeh Rahbarizadeh, Davoud Ahmadvand, Hamid Reza Madaah Hosseini) declare to have no competing interests.

Ethical Approval

This article does not contain any studies with human participants and animals performed by any of the authors.

Funding

This paper was supported by Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran and School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran reference 16550.

Author information

Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. BOX. 14115-331, Tehran, Iran

    Sepideh Khaleghi & Fatemeh Rahbarizadeh

  2. School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

    Davoud Ahmadvand

  3. Materials Science and Engineering Department, Sharif University of Technology, Azadi Avenue, P.O. BOX. 11155-9466, Tehran, Iran

    Hamid Reza Madaah Hosseini

Authors
  1. Sepideh Khaleghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatemeh Rahbarizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Davoud Ahmadvand
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hamid Reza Madaah Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fatemeh Rahbarizadeh.

Additional information

Associate Editor Partha Roy oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khaleghi, S., Rahbarizadeh, F., Ahmadvand, D. et al. Anti-HER2 VHH Targeted Magnetoliposome for Intelligent Magnetic Resonance Imaging of Breast Cancer Cells. Cel. Mol. Bioeng. 10, 263–272 (2017). https://doi.org/10.1007/s12195-017-0481-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-017-0481-z

Keywords

Search

Navigation