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Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier

Imaging-guided delivery is developed for hydrophobic drugs, and to a much lesser extent, hydrophilic ones. In this work we have designed a novel strategy for real-time monitoring of hydrophilic drug delivery. Traditionally, the drug and the dye are covalently attached to a nanocarrier or are electro...

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Autores principales: Zakharenkova, Sofia A., Lebedeva, Marina I., Lebedeva, Alexandra N., Doroshenko, Irina A., Vlasova, Ksenya Yu, Bartoshevich, Anastasiya A., Senyavin, Vladimir M., Abramchuk, Sergey S., Krivtsov, George G., Ezhov, Alexander A., Podrugina, Tatyana A., Klyachko, Natalia L., Beklemishev, Mikhail K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703758/
https://www.ncbi.nlm.nih.gov/pubmed/34946504
http://dx.doi.org/10.3390/molecules26247426
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author Zakharenkova, Sofia A.
Lebedeva, Marina I.
Lebedeva, Alexandra N.
Doroshenko, Irina A.
Vlasova, Ksenya Yu
Bartoshevich, Anastasiya A.
Senyavin, Vladimir M.
Abramchuk, Sergey S.
Krivtsov, George G.
Ezhov, Alexander A.
Podrugina, Tatyana A.
Klyachko, Natalia L.
Beklemishev, Mikhail K.
author_facet Zakharenkova, Sofia A.
Lebedeva, Marina I.
Lebedeva, Alexandra N.
Doroshenko, Irina A.
Vlasova, Ksenya Yu
Bartoshevich, Anastasiya A.
Senyavin, Vladimir M.
Abramchuk, Sergey S.
Krivtsov, George G.
Ezhov, Alexander A.
Podrugina, Tatyana A.
Klyachko, Natalia L.
Beklemishev, Mikhail K.
author_sort Zakharenkova, Sofia A.
collection PubMed
description Imaging-guided delivery is developed for hydrophobic drugs, and to a much lesser extent, hydrophilic ones. In this work we have designed a novel strategy for real-time monitoring of hydrophilic drug delivery. Traditionally, the drug and the dye are covalently attached to a nanocarrier or are electrostatically adsorbed. Recently, we found an efficient way to bind the drug by ion-paring with an appropriate counter-ion to form the aggregate that embeds a hydrophobic dye with a considerable fluorescence enhancement. We synthesized a series of carbocyanine dyes of hydrophobicity sufficient for solubilization in hydrophobic ion pairs, which restores their emission in the near-infrared (NIR) region upon the formation of the ternary aggregates. To avoid using toxic surfactants, we applied an amphiphilic polymer-oligomer poly(hexamethylene guanidine) (PHMG) as a counter-ion. Сeftriaxone was used as a model hydrophilic drug ensuring the highest fluorescent signal. The so-formed drug–counter-ion–dye aggregates were encapsulated into a cross-linked maleated chitosan carrier. Confocal laser scanning microscopy (CLSM) studies have demonstrated internalization of the encapsulated model drug by breast adenocarcinoma cells at 40 min after treatment. These results suggest the potential application of hydrophobic ion pairs containing an NIR dye in imaging-guided delivery of hydrophilic compounds.
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spelling pubmed-87037582021-12-25 Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier Zakharenkova, Sofia A. Lebedeva, Marina I. Lebedeva, Alexandra N. Doroshenko, Irina A. Vlasova, Ksenya Yu Bartoshevich, Anastasiya A. Senyavin, Vladimir M. Abramchuk, Sergey S. Krivtsov, George G. Ezhov, Alexander A. Podrugina, Tatyana A. Klyachko, Natalia L. Beklemishev, Mikhail K. Molecules Article Imaging-guided delivery is developed for hydrophobic drugs, and to a much lesser extent, hydrophilic ones. In this work we have designed a novel strategy for real-time monitoring of hydrophilic drug delivery. Traditionally, the drug and the dye are covalently attached to a nanocarrier or are electrostatically adsorbed. Recently, we found an efficient way to bind the drug by ion-paring with an appropriate counter-ion to form the aggregate that embeds a hydrophobic dye with a considerable fluorescence enhancement. We synthesized a series of carbocyanine dyes of hydrophobicity sufficient for solubilization in hydrophobic ion pairs, which restores their emission in the near-infrared (NIR) region upon the formation of the ternary aggregates. To avoid using toxic surfactants, we applied an amphiphilic polymer-oligomer poly(hexamethylene guanidine) (PHMG) as a counter-ion. Сeftriaxone was used as a model hydrophilic drug ensuring the highest fluorescent signal. The so-formed drug–counter-ion–dye aggregates were encapsulated into a cross-linked maleated chitosan carrier. Confocal laser scanning microscopy (CLSM) studies have demonstrated internalization of the encapsulated model drug by breast adenocarcinoma cells at 40 min after treatment. These results suggest the potential application of hydrophobic ion pairs containing an NIR dye in imaging-guided delivery of hydrophilic compounds. MDPI 2021-12-07 /pmc/articles/PMC8703758/ /pubmed/34946504 http://dx.doi.org/10.3390/molecules26247426 Text en © 2021 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
Zakharenkova, Sofia A.
Lebedeva, Marina I.
Lebedeva, Alexandra N.
Doroshenko, Irina A.
Vlasova, Ksenya Yu
Bartoshevich, Anastasiya A.
Senyavin, Vladimir M.
Abramchuk, Sergey S.
Krivtsov, George G.
Ezhov, Alexander A.
Podrugina, Tatyana A.
Klyachko, Natalia L.
Beklemishev, Mikhail K.
Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier
title Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier
title_full Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier
title_fullStr Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier
title_full_unstemmed Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier
title_short Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier
title_sort imaging-guided delivery of a hydrophilic drug to eukaryotic cells based on its hydrophobic ion pairing with poly(hexamethylene guanidine) in a maleated chitosan carrier
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703758/
https://www.ncbi.nlm.nih.gov/pubmed/34946504
http://dx.doi.org/10.3390/molecules26247426
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