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Article Open Access

Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin

  • Authors:
    • Anna Andreevna Nemudraya
    • Elena Vladimirovna Kuligina
    • Alexandr Alexeevich Ilyichev
    • Alexandr Sergeevich Fomin
    • Grigory Alexandrovich Stepanov
    • Anna Valentinovna Savelyeva
    • Olga Alexandrovna Koval
    • Vladimir Alexandrovich Richter
  • View Affiliations / Copyright

    Affiliations: Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of The Russian Academy of Sciences, 630090 Novosibirsk, Russia, Department of Bioengineering, State Research Center of Virology and Biotechnology VECTOR, 630559 Koltsovo, Russia
    Copyright: © Nemudraya et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4547-4555
    |
    Published online on: October 14, 2016
       https://doi.org/10.3892/ol.2016.5266
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Abstract

It has been previously demonstrated that lactaptin, the proteolytic fragment of human milk protein κ‑casein, induces the death of various cultured cancer cells. The recombinant analog of lactaptin, RL2, effectively induces the apoptosis of mouse hepatocarcinoma‑1 (HA‑1) tumor cells in vitro and suppress the growth of HA‑1 tumors and metastases in vivo. The antitumor drug Lactaptin developed on the basis of RL2 has been successful in preclinical trials. Lactaptin shows its efficiency in relation to mouse and human cancer cells and tumors. However, Lactaptin, as with the majority of protein‑based therapeutic drugs, is distributed evenly throughout the organism, which reduces its antitumor efficacy. To develop the targeted delivery of lactaptin, the present study selected tumor‑specific peptides by screening a phage display peptide library in vivo on A/Sn strain mice with subcutaneously transplanted HA‑1 cells. Two genetic constructs were made for the production of recombinant fusion proteins composed of RL2 and the selected tumor‑targeting peptide. In vitro experiments involving HA‑1, MDA‑MB‑231 and MCF‑7 cells cultures demonstrated that the fusion proteins induce apoptotic death in mouse and human tumor cells, as with RL2. The in vivo experiments involving the mouse HA‑1 tumor model demonstrated that the tumor fluorescence intensity of the Cy5‑fusion protein conjugates is higher than that of RL2‑Cy5. As conjugation of the tumor‑specific peptides to RL2 provided retention of RL2 in the tumor tissues, fusion proteins composed of lactaptin and peptides specific for human tumors are deemed promising to improve the antitumor efficiency of lactaptin.
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Copy and paste a formatted citation
Spandidos Publications style
Nemudraya AA, Kuligina EV, Ilyichev AA, Fomin AS, Stepanov GA, Savelyeva AV, Koval OA and Richter VA: Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin. Oncol Lett 12: 4547-4555, 2016.
APA
Nemudraya, A.A., Kuligina, E.V., Ilyichev, A.A., Fomin, A.S., Stepanov, G.A., Savelyeva, A.V. ... Richter, V.A. (2016). Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin. Oncology Letters, 12, 4547-4555. https://doi.org/10.3892/ol.2016.5266
MLA
Nemudraya, A. A., Kuligina, E. V., Ilyichev, A. A., Fomin, A. S., Stepanov, G. A., Savelyeva, A. V., Koval, O. A., Richter, V. A."Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin". Oncology Letters 12.6 (2016): 4547-4555.
Chicago
Nemudraya, A. A., Kuligina, E. V., Ilyichev, A. A., Fomin, A. S., Stepanov, G. A., Savelyeva, A. V., Koval, O. A., Richter, V. A."Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin". Oncology Letters 12, no. 6 (2016): 4547-4555. https://doi.org/10.3892/ol.2016.5266
Copy and paste a formatted citation
x
Spandidos Publications style
Nemudraya AA, Kuligina EV, Ilyichev AA, Fomin AS, Stepanov GA, Savelyeva AV, Koval OA and Richter VA: Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin. Oncol Lett 12: 4547-4555, 2016.
APA
Nemudraya, A.A., Kuligina, E.V., Ilyichev, A.A., Fomin, A.S., Stepanov, G.A., Savelyeva, A.V. ... Richter, V.A. (2016). Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin. Oncology Letters, 12, 4547-4555. https://doi.org/10.3892/ol.2016.5266
MLA
Nemudraya, A. A., Kuligina, E. V., Ilyichev, A. A., Fomin, A. S., Stepanov, G. A., Savelyeva, A. V., Koval, O. A., Richter, V. A."Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin". Oncology Letters 12.6 (2016): 4547-4555.
Chicago
Nemudraya, A. A., Kuligina, E. V., Ilyichev, A. A., Fomin, A. S., Stepanov, G. A., Savelyeva, A. V., Koval, O. A., Richter, V. A."Selection of antitumor displayed peptides for the specific delivery of the anticancer drug lactaptin". Oncology Letters 12, no. 6 (2016): 4547-4555. https://doi.org/10.3892/ol.2016.5266
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