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Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe
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 de...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955029/ https://www.ncbi.nlm.nih.gov/pubmed/35328540 http://dx.doi.org/10.3390/ijms23063119 |
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author | Yabbarov, Nikita Nikolskaya, Elena Sokol, Maria Mollaeva, Mariia Chirkina, Margarita Seregina, Irina Gulyaev, Mikhail Pirogov, Yury Petrov, Rem |
author_facet | Yabbarov, Nikita Nikolskaya, Elena Sokol, Maria Mollaeva, Mariia Chirkina, Margarita Seregina, Irina Gulyaev, Mikhail Pirogov, Yury Petrov, Rem |
author_sort | Yabbarov, Nikita |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8955029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89550292022-03-26 Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe Yabbarov, Nikita Nikolskaya, Elena Sokol, Maria Mollaeva, Mariia Chirkina, Margarita Seregina, Irina Gulyaev, Mikhail Pirogov, Yury Petrov, Rem Int J Mol Sci Article 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. MDPI 2022-03-14 /pmc/articles/PMC8955029/ /pubmed/35328540 http://dx.doi.org/10.3390/ijms23063119 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yabbarov, Nikita Nikolskaya, Elena Sokol, Maria Mollaeva, Mariia Chirkina, Margarita Seregina, Irina Gulyaev, Mikhail Pirogov, Yury Petrov, Rem Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe |
title | Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe |
title_full | Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe |
title_fullStr | Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe |
title_full_unstemmed | Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe |
title_short | Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe |
title_sort | synergetic enhancement of tumor double-targeted mri nano-probe |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955029/ https://www.ncbi.nlm.nih.gov/pubmed/35328540 http://dx.doi.org/10.3390/ijms23063119 |
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