Russian Chemical Bulletin, volume 69, issue 4, pages 793-803
Cellular internalization of targeted and non-targeted delivery systems for contrast agents based on polyamidoamine dendrimers
Sokol M B
1
,
Faustova M R
1, 2
,
Nikolskaya E D
1, 3
,
Zhunina O A
1, 3
,
Fomicheva M V
1
,
Petrov R. V.
4
,
Yabbarov N G
1, 3
1
Russian Research Center for Molecular Diagnostics and Therapy, Moscow, Russian Federation
|
3
Publication type: Journal Article
Publication date: 2020-04-26
Journal:
Russian Chemical Bulletin
Quartile SCImago
Q3
Quartile WOS
Q3
Impact factor: 1.7
ISSN: 10665285, 15739171
General Chemistry
Abstract
New high-molecular-weight contrast agents based on polyamidoamine (PAMAM) dendrimers for targeted imaging of malignant tumors characterized by overexpression of human epidermal growth factor receptor (EGFR) and human alpha-fetoprotein receptor (RECAF) were designed. Conjugates of second (G2) and third (G3) generation polyamidoamine dendrimers with 1,4,7,10-tetraazocyclodecane-1,4,7,10-tetraacetic acid (DOTA) were obtained. The quantitative composition of the conjugates was determined by 1 HNMR spectroscopy. It was shown that four out of the 16 terminal NH 2 groups in G2-DOTA and nine out of the 32 groups in G3-DOTA were modified with DOTA. The morphology, size, and charge of the synthesized macromolecules were characterized by dynamic light scattering and electrophoresis. Gadolinium(III) was loaded into the conjugates and the Gd content was determined by atomic emission spectroscopy. For increasing the selectivity of accumulation in the tumor cells, two recombinant proteins able to bind selectively to EGFR and RECAF, namely, human recombinant epidermal growth factor (rEGF) and human recombinant 3rd domain of alpha-fetoprotein (3dAFPpG), were conjugated with G2 and G3 dendrimers. The conjugates containing vector molecules were mainly accumulated via clathrin-dependent endocytosis, whereas G2-DOTA and G3-DOTA were absorbed via caveolin-dependent endocytosis and macropinocytosis. The dendrimer conjugates with vector molecules were intensely accumulated in A549 cells characterized by high expression of EGFR (Herl) and RECAF, whereas the accumulation of conjugates in the control K562 cells (with low expression of Her1) and in the CD14 − population of human unstimulated mononuclear white blood cells was insignificant. The 3dAFPpG-conjugated dendrimers were partly recycled. All synthesized conjugates had a rather low toxicity in the range of 350–450 µmol L −1 (IC 50 ).
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Sokol M. B. et al. Cellular internalization of targeted and non-targeted delivery systems for contrast agents based on polyamidoamine dendrimers // Russian Chemical Bulletin. 2020. Vol. 69. No. 4. pp. 793-803.
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Sokol M. B., Faustova M. R., Nikolskaya E. D., Zhunina O. A., Fomicheva M. V., Petrov R. V., Yabbarov N. G. Cellular internalization of targeted and non-targeted delivery systems for contrast agents based on polyamidoamine dendrimers // Russian Chemical Bulletin. 2020. Vol. 69. No. 4. pp. 793-803.
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TY - JOUR
DO - 10.1007/s11172-020-2835-2
UR - https://doi.org/10.1007%2Fs11172-020-2835-2
TI - Cellular internalization of targeted and non-targeted delivery systems for contrast agents based on polyamidoamine dendrimers
T2 - Russian Chemical Bulletin
AU - Faustova, M R
AU - Nikolskaya, E D
AU - Zhunina, O A
AU - Fomicheva, M V
AU - Petrov, R. V.
AU - Yabbarov, N G
AU - Sokol, M B
PY - 2020
DA - 2020/04/26 00:00:00
PB - Springer Nature
SP - 793-803
IS - 4
VL - 69
SN - 1066-5285
SN - 1573-9171
ER -
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@article{2020_Sokol,
author = {M R Faustova and E D Nikolskaya and O A Zhunina and M V Fomicheva and R. V. Petrov and N G Yabbarov and M B Sokol},
title = {Cellular internalization of targeted and non-targeted delivery systems for contrast agents based on polyamidoamine dendrimers},
journal = {Russian Chemical Bulletin},
year = {2020},
volume = {69},
publisher = {Springer Nature},
month = {apr},
url = {https://doi.org/10.1007%2Fs11172-020-2835-2},
number = {4},
pages = {793--803},
doi = {10.1007/s11172-020-2835-2}
}
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Sokol, M. B., et al. “Cellular internalization of targeted and non-targeted delivery systems for contrast agents based on polyamidoamine dendrimers.” Russian Chemical Bulletin, vol. 69, no. 4, Apr. 2020, pp. 793-803. https://doi.org/10.1007%2Fs11172-020-2835-2.