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Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe

Тип документаJournal Article
Дата публикации2022-03-14
Название журналаInternational Journal of Molecular Sciences
ИздательMultidisciplinary Digital Publishing Institute (MDPI)
Квартиль по SCImagoQ1
Квартиль по Web of ScienceQ1
Импакт-фактор 20216.21
ISSN16616596, 14220067
Catalysis
Organic Chemistry
Inorganic Chemistry
Physical and Theoretical Chemistry
Computer Science Applications
Spectroscopy
Molecular Biology
General Medicine
Краткое описание

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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1. Yabbarov N. и др. Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe // International Journal of Molecular Sciences. 2022. Т. 23. № 6. С. 3119.
RIS |
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TY - JOUR

DO - 10.3390/ijms23063119

UR - http://dx.doi.org/10.3390/ijms23063119

TI - Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe

T2 - International Journal of Molecular Sciences

AU - Yabbarov, Nikita

AU - Nikolskaya, Elena

AU - Sokol, Maria

AU - Mollaeva, Mariia

AU - Chirkina, Margarita

AU - Seregina, Irina

AU - Gulyaev, Mikhail

AU - Pirogov, Yury

AU - Petrov, Rem

PY - 2022

DA - 2022/03/14

PB - MDPI AG

SP - 3119

IS - 6

VL - 23

SN - 1422-0067

ER -

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@article{Yabbarov_2022,

doi = {10.3390/ijms23063119},

url = {https://doi.org/10.3390%2Fijms23063119},

year = 2022,

month = {mar},

publisher = {{MDPI} {AG}},

volume = {23},

number = {6},

pages = {3119},

author = {Nikita Yabbarov and Elena Nikolskaya and Maria Sokol and Mariia 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}

}

MLA
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Yabbarov, Nikita, et al. “Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe.” International Journal of Molecular Sciences, vol. 23, no. 6, Mar. 2022, p. 3119. Crossref, https://doi.org/10.3390/ijms23063119.