Open Access
Open access
volume 23 issue 6 pages 3119

Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe

Publication typeJournal Article
Publication date2022-03-14
scimago Q1
wos Q1
SJR1.273
CiteScore9.0
Impact factor4.9
ISSN16616596, 14220067
PubMed ID:  35328540
Catalysis
Organic Chemistry
Inorganic Chemistry
Physical and Theoretical Chemistry
Computer Science Applications
Spectroscopy
Molecular Biology
General Medicine
Abstract

The conventional targeted delivery of chemotherapeutic and diagnostic agents utilizing nanocarriers is a promising approach for cancer theranostics. Unfortunately, this approach often faces hindered tumor access that decreases the therapeutic index and limits the further clinical translation of a developing drug. Here, we demonstrated a strategy of simultaneously double-targeting the drug to two distinct cites of tumor tissue: the tumor endothelium and cell surface receptors. We used fourth-generation polyamideamine dendrimers modified with a chelated Gd and functionalized with selectin ligand and alpha-fetoprotein receptor-binding peptide. According to the proposed strategy, IELLQAR peptide promotes the conjugate recruitment to the tumor inflammatory microenvironment and enhances extravasation through the interaction of nanodevice with P- and E-selectins expressed by endothelial cells. The second target moiety—alpha-fetoprotein receptor-binding peptide—enhances drug internalization into cancer cells and the intratumoral retention of the conjugate. The final conjugate contained 18 chelated Gd ions per dendrimer, characterized with a 32 nm size and a negative surface charge of around 18 mV. In vitro contrasting properties were comparable with commercially available Gd-chelate: r1 relaxivity was 3.39 for Magnevist and 3.11 for conjugate; r2 relaxivity was 5.12 for Magnevist and 4.81 for conjugate. By utilizing this dual targeting strategy, we demonstrated the increment of intratumoral accumulation, and a remarkable enhancement of antitumor effect, resulting in high-level synergy compared to monotargeted conjugates. In summary, the proposed strategy utilizing tumor tissue double-targeting may contribute to an enhancement in drug and diagnostic accumulation in aggressive tumors.

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GOST Copy
Yabbarov N. G. et al. Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe // International Journal of Molecular Sciences. 2022. Vol. 23. No. 6. p. 3119.
GOST all authors (up to 50) Copy
Yabbarov N. G., Nikolskaya E. D., Sokol M., Mollaeva M. R., Chirkina M., Seregina I., Gulyaev M., Pirogov Y., Petrov R. Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe // International Journal of Molecular Sciences. 2022. Vol. 23. No. 6. p. 3119.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.3390/ijms23063119
UR - https://www.mdpi.com/1422-0067/23/6/3119
TI - Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe
T2 - International Journal of Molecular Sciences
AU - Yabbarov, Nikita G
AU - Nikolskaya, Elena D
AU - Sokol, Maria
AU - Mollaeva, Mariia R
AU - Chirkina, Margarita
AU - Seregina, Irina
AU - Gulyaev, Mikhail
AU - Pirogov, Yury
AU - Petrov, Rem
PY - 2022
DA - 2022/03/14
PB - MDPI
SP - 3119
IS - 6
VL - 23
PMID - 35328540
SN - 1661-6596
SN - 1422-0067
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2022_Yabbarov,
author = {Nikita G Yabbarov and Elena D Nikolskaya and Maria Sokol and Mariia R Mollaeva and Margarita Chirkina and Irina Seregina and Mikhail Gulyaev and Yury Pirogov and Rem Petrov},
title = {Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe},
journal = {International Journal of Molecular Sciences},
year = {2022},
volume = {23},
publisher = {MDPI},
month = {mar},
url = {https://www.mdpi.com/1422-0067/23/6/3119},
number = {6},
pages = {3119},
doi = {10.3390/ijms23063119}
}
MLA
Cite this
MLA Copy
Yabbarov, Nikita G., et al. “Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe.” International Journal of Molecular Sciences, vol. 23, no. 6, Mar. 2022, p. 3119. https://www.mdpi.com/1422-0067/23/6/3119.