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Targeted delivery of quantum dots to the HER2-expressing tumor using recombinant antibodies

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Abstract

Targeted delivery of semiconductor quantum dots (QDs) to tumors overexpressing HER2 cancer marker has been demonstrated on immunocompromised mice bearing human breast cancer xenografts. To obtain targeted QDs complexes we applied the approach based on the use of protein adaptor system, RNAase barnase and its inhibitor barstar. Specific binding to target cancer marker was achieved through bivalent fusion protein containing two fragments of 4D5scFv recombinant antibody and a fragment of barnase. QDs were conjugated to barstar, and final assembly of targeted complexes was obtained through non-covalent specific interaction of barstar, attached to QD, and barnase, that is part of the recombinant targeting protein. The efficient delivery of QDs to HER2-expressing tumor demonstrates the possibilities and prospects of the approach for targeted delivery of nanoparticles to cancer cells in vivo as the way to improve the efficiency of diagnosis and promote development of therapies based on the use of nanoparticles.

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Abbreviations

Bn:

barnase

Bs:

barstar

EDC:

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

IPTG:

isopropyl-β-D-1-thiogalactopyranoside

HER2:

human epithelial growth factor receptor 2

PBS:

phosphate-buffered saline

QD:

quantum dot

PEG:

polyethylene glycol

scFv:

single-chain variable fragment

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Authors and Affiliations

  1. Lobachevsky State University, pr. Gagarina 23, Nizhny Novgorod, 603950, Russia

    I. V. Balalaeva, T. A. Zdobnova, E. A. Sokolova & S. M. Deyev

  2. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia

    S. M. Deyev

Authors
  1. I. V. Balalaeva
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  2. T. A. Zdobnova
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  3. E. A. Sokolova
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  4. S. M. Deyev
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Corresponding author

Correspondence to I. V. Balalaeva.

Additional information

Proceedings of VII Russian Symposium “Proteins and Peptides,” Novosibirsk, July 12–17, 2015.

Original Russian Text © I.V. Balalaeva, T.A. Zdobnova, E.A. Sokolova, S.M. Deyev, 2015, published in Bioorganicheskaya Khimiya, 2015, Vol. 41, No. 5, pp. 599–605.

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Balalaeva, I.V., Zdobnova, T.A., Sokolova, E.A. et al. Targeted delivery of quantum dots to the HER2-expressing tumor using recombinant antibodies. Russ J Bioorg Chem 41, 536–542 (2015). https://doi.org/10.1134/S1068162015050040

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  • DOI: https://doi.org/10.1134/S1068162015050040

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