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Chitosan nanoparticles targeted to the tumor-associated ganglioside GD2

Abstract

Methodological approaches to the creation of nanoparticles based on chitosan derivatives and targeted to the GD2-positive tumor cells were developed. The GD2-specific monoclonal antibodies and their Fab-fragments and scFv-fragments were obtained and studied as vector molecules. Various methods for covalent conjugation of these molecules to the nanoparticles were also studied. It was shown that site-specific conjugation of scFv-fragments of GD2-specific antibodies to the chitosan nanoparticles by using a reagent BMPS is the optimal approach to create targeted chitosan-based nanoparticles directed to tumor-associated ganglioside GD2.

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Abbreviations

anti-GD2-mAbs:

GD2-specific monoclonal antibodies

BMPS:

N-(β-maleimidopropionyl)succinimide

CDI-method:

the carbodiimide method

EDC-1:

ethyl-3-(3-dimethylaminopropyl)carbodiimide

IPTG:

isopropyl-β-D-1- thiogalactopyranoside

Fab:

the antigen-binding fragment of an antibody

FBS:

fetal bovine serum

FITC:

fluorescein-5-isothiocyanate

HRP:

horseradish peroxidase

miR:

small noncoding RNA molecules

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NHS:

N-hydroxysuccinimide

PBS:

phosphate buffered saline

PI:

propidium iodide

scFv:

single-chain variable fragments of antibodies

siRNA:

small interfering RNA

TCEP:

tris(2-carboxyethyl)phosphine

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Correspondence to R. V. Kholodenko.

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Original Russian Text © A.A. Zubareva, A.A. Boyko, I.V. Kholodenko, F.N. Rozov, M.V. Larina, T.K. Aliev, I.I. Doronin, P.A. Vishnyakova, I.M. Molotkovskaya, R.V. Kholodenko, 2016, published in Bioorganicheskaya Khimiya, 2016, Vol. 42, No. 5, pp. 588–602.

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Zubareva, A.A., Boyko, A.A., Kholodenko, I.V. et al. Chitosan nanoparticles targeted to the tumor-associated ganglioside GD2. Russ J Bioorg Chem 42, 532–545 (2016). https://doi.org/10.1134/S1068162016050150

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  • DOI: https://doi.org/10.1134/S1068162016050150

Keywords

  • ganglioside GD2
  • tumor-associated gangliosides
  • targeted nanoparticles
  • cell death
  • monoclonal antibodies
  • Fab-fragments
  • scFv-fragments