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Targeted delivery of doxorubicin: Drug delivery system based on PAMAM dendrimers

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Abstract

Polyamidoamine (PAMAM) dendrimers of the second generation (G2) are branched polymers containing 16 surface amino groups that allow them to be used as universal carriers on creating systems for drug delivery. G2 labeled with fluorescein isothiocyanate (FITC) efficiently bound with the surface of tumor cells at 4°C and was absorbed by the cells at 37°C. The covalent binding to G2-FITC of a vector protein, a recombinant fragment of the human alpha-fetoprotein receptor-binding domain (rAFP3D), increased the binding and endocytosis efficiency more than threefold. Covalent conjugates of G2 with doxorubicin (Dox) obtained by acid-labile linking of cis-aconitic anhydride (CAA) without the vector protein (G2-Dox) and with the vector protein rAFP3D (rAFP3D-G2-Dox) were accumulated by the tumor cells with high efficiency. However, a selective effect was observed only in rAFP3D-G2-Dox, which also demonstrated high cytotoxic activity against the human ovarian adenocarcinoma SKOV3 cells and low cytotoxicity against human peripheral blood lymphocytes. Based on these results, rAFP3D-G2 conjugate is promising for selective delivery of antitumor drugs.

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References

  1. Tomalia, D. A., Baker, H., Dewald, J., Hall, M., Kallos, G., Martin, S., Roeck, J., Ryder, J., and Smith, P. (1985) Polymer J., 17, 117–132.

    Article  CAS  Google Scholar 

  2. Aulenta, F., Hayes, W., and Rannard, S. (2003) Eur. Polymer J., 39, 1741–1771.

    Article  CAS  Google Scholar 

  3. Svenson, S., and Tomalia, D. A. (2005) Adv. Drug Deliv. Rev., 57, 2106–2129.

    Article  PubMed  CAS  Google Scholar 

  4. Boas, U., and Heegaard, P. M. H. (2004) Chem. Soc. Rev., 33, 43–63.

    Article  PubMed  CAS  Google Scholar 

  5. Sampathkumar, S.-G., and Yarema, K. J. (2007) in Nanotechnologies for the Life Sciences, Wiley-VCH Verlag GmbH & Co. KGaA.

    Google Scholar 

  6. Sinha, B. K., and Politi, P. M. (1990) Cancer Chemother. Biol. Response Modif., 11, 45–57.

    PubMed  CAS  Google Scholar 

  7. Agarwal, A., Saraf, S., Asthana, A., Gupta, U., Gajbhiye, V., and Jain, N. K. (2008) Int. J. Pharmac., 350, 3–13.

    Article  CAS  Google Scholar 

  8. Ward, B. B., Dunham, T., Majoros, I. J., and Baker, J. R., Jr. (2011) J. Oral Maxillofac. Surg., 69, 2452–2459.

    Article  PubMed  Google Scholar 

  9. Chen, K., and Mitchell, D. (2012) in Glioma (Yamanaka, R., ed.) Springer, New York, Vol. 746, pp. 121–141.

  10. Miyano, T., Wijagkanalan, W., Kawakami, S., Yamashita, F., and Hashida, M. (2010) Mol. Pharmac., 7, 1318–1327.

    Article  CAS  Google Scholar 

  11. Moro, R., Tcherkassova, J., and Song, E. (2005) IVD Technology [Online] Available at: http://www.ivdtechnology.com/article/new-broad-spectrum-cancer-marker.

    Google Scholar 

  12. Nitsvetov, M. B., Moskaleva, E. Y., Posypanova, G. A., Makarova, O. V., Stepanov, V. A., Rogov, K. A., Koromyslova, I. A., Karaulov, A. V., Severin, S. E., and Severin, E. S. (2005) Immunologiya, 26, 122–125.

    Google Scholar 

  13. Moskaleva, E. Y., Posypanova, G. A., Koromyslova, I. A., Shmyrev, I. I., Krivonos, A. V., Myagkikh, I. V., Feldman, N. B., Finakova, G. V., Katukov, V. Y., Luzhkov, Y. M., Nakachian, R., Andreani, J., Severin, E. S., and Severin, S. E. (1996) Tumor Target., 2, 299–306.

    Google Scholar 

  14. Severin, S. E., Posypanova, G. A., Katukov, V. Y., Shmyrev, I. I., Luzhkov, Y. M., Gerasimova, G. K., Zhukova, O. S., Vorozhtsov, G. N., Kaliya, O. L., Lukyanets, E. A., and Severin, E. S. (1997) Biochem. Mol. Biol. Int., 43, 1081–1089.

    PubMed  CAS  Google Scholar 

  15. Posypanova, G. A., Gorokhovets, N. V., Makarov, V. A., Savvateeva, L. V., Kireeva, N. N., Severin, S. E., and Severin, E. S. (2008) J. Drug Target., 16, 321–328.

    Article  PubMed  CAS  Google Scholar 

  16. Godovannyi, A. V., Savvateeva, M. V., Sotnichenko, A. I., Yabbarov, N. S., Klimova, O. V., Gnuchev, H. V., and Severin, S. E. (2011) Mol. Med., 1, 44–48.

    Google Scholar 

  17. Sambrook, J., and Russell, D. G. (2001) Molecular Cloning: A Laboratory Manual, 3rd Edn., Cold Spring Harbor Laboratory Press, New York.

    Google Scholar 

  18. Sharapova, O. A., Yurkova, M. S., Laurinavichyute, D. K., Andronova, S. M., Fedorov, A. N., Severin, S. E., and Severin, E. S. (2011) J. Chromatogr. A, 1218, 5115–5119.

    Article  PubMed  CAS  Google Scholar 

  19. Perumal, O. P., Inapagolla, R., Kannan, S., and Kannan, R. M. (2008) Biomaterials, 29, 3469–3476.

    Article  PubMed  CAS  Google Scholar 

  20. Butcher, E. C., and Weissman, I. L. (1980) J. Immunol. Meth., 37, 97–108.

    Article  CAS  Google Scholar 

  21. Tian, Y., Bromberg, L., Lin, S. N., Alan Hatton, T., and Tam, K. C. (2007) J. Contr. Rel., 121, 137–145.

    Article  CAS  Google Scholar 

  22. Boyum, A. (1968) Scand. J. Clin. Lab. Invest., 97(Suppl.), 77–89.

    CAS  Google Scholar 

  23. Denizot, F., and Lang, R. (1986) J. Immunol. Meth., 89, 271–277.

    Article  CAS  Google Scholar 

  24. Torres, J. M., Laborda, J., Naval, J., Darracq, N., Calvo, M., Mishal, Z., and Uriel, J. (1989) Mol. Immunol., 26, 851–857.

    Article  PubMed  CAS  Google Scholar 

  25. Kitchens, K. M., Kolhatkar, R. B., Swaan, P. W., and Ghandehari, H. (2008) Mol. Pharm., 5, 364–369.

    Article  PubMed  CAS  Google Scholar 

  26. Saovapakhiran, A., D’Emanuele, A., Attwood, D., and Penny, J. (2009) Bioconj. Chem., 20, 693–701.

    Article  CAS  Google Scholar 

  27. Qi, R., Mullen, D. G., Baker, J. R., and Banaszak Holl, M. M. (2009) Mol. Pharm., 7, 267–279.

    Article  Google Scholar 

  28. Kitchens, K. M., Foraker, A. B., Kolhatkar, R. B., Swaan, P. W., and Ghandehari, H. (2007) Pharm. Res., 24, 2138–2145.

    Article  PubMed  CAS  Google Scholar 

  29. Seib, F. P., Jones, A. T., and Duncan, R. (2007) J. Contr. Rel., 117, 291–300.

    Article  CAS  Google Scholar 

  30. Albertazzi, L., Serresi, M., Albanese, A., and Beltram, F. (2010) Mol. Pharm., 7, 680–688.

    Article  PubMed  CAS  Google Scholar 

  31. Severin, S. E., Posypanova, G. A., Sotnichenko, A. I., Moskaleva, E. Y., Feldman, N. B., Grigoriev, M. I., Severin, E. S., and Petrov, R. V. (1999) Dokl. Akad. Nauk SSSR, 366, 561–564.

    CAS  Google Scholar 

  32. Sharapova, O. A., Posdnyakova, N. V., Laurinavichyute, D. K., Yurkova, M. S., Posypanova, G. A., Andronova, S. M., Fedorov, A. N., Severin, S. E., and Severin, E. S. (2010) Bioorg. Khim., 36, 760–768.

    PubMed  CAS  Google Scholar 

  33. Esteban, C., Trojan, J., Macho, A., Mishal, Z., Lafarge-Frayssinet, C., and Uriel, J. (1993) Leukemia, 7, 1807–1816.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Bioengineering Center, Russian Academy of Sciences, pr. 60-letiya Oktyabrya 7/1, 117312, Moscow, Russia

    N. G. Yabbarov

  2. National Research Center “Kurchatov Institute”, pl. Akademika Kurchatova 1, 123182, Moscow, Russia

    G. A. Posypanova & O. N. Popova

  3. Russian Research Center of Molecular Diagnostics and Therapy, Simferopolsky Bulvar 8, 117149, Moscow, Russia

    E. A. Vorontsov & E. S. Severin

Authors
  1. N. G. Yabbarov
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  2. G. A. Posypanova
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  3. E. A. Vorontsov
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  4. O. N. Popova
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  5. E. S. Severin
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Corresponding author

Correspondence to N. G. Yabbarov.

Additional information

Original Russian Text © N. G. Yabbarov, G. A. Posypanova, E. A. Vorontsov, O. N. Popova, E. S. Severin, 2013, published in Biokhimiya, 2013, Vol. 78, No. 8, pp. 1128–1140.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM12-309, June 23, 2013.

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Yabbarov, N.G., Posypanova, G.A., Vorontsov, E.A. et al. Targeted delivery of doxorubicin: Drug delivery system based on PAMAM dendrimers. Biochemistry Moscow 78, 884–894 (2013). https://doi.org/10.1134/S000629791308004X

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  • DOI: https://doi.org/10.1134/S000629791308004X

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