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Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent

As desirable contrast agents for magnetic resonance imaging (MRI), ultrasmall superparamagnetic iron oxides (USPIOs) are required to exhibit both low cytotoxicity and specific targetability besides superparamagnetism to achieve better imaging contrast at lower dose, and cladding with biocompatible p...

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Autores principales: Yin, Jie, Yin, Guangfu, Pu, Ximing, Huang, Zhongbing, Yao, Dajin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065400/
https://www.ncbi.nlm.nih.gov/pubmed/35519366
http://dx.doi.org/10.1039/c9ra02636c
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author Yin, Jie
Yin, Guangfu
Pu, Ximing
Huang, Zhongbing
Yao, Dajin
author_facet Yin, Jie
Yin, Guangfu
Pu, Ximing
Huang, Zhongbing
Yao, Dajin
author_sort Yin, Jie
collection PubMed
description As desirable contrast agents for magnetic resonance imaging (MRI), ultrasmall superparamagnetic iron oxides (USPIOs) are required to exhibit both low cytotoxicity and specific targetability besides superparamagnetism to achieve better imaging contrast at lower dose, and cladding with biocompatible polymers and modification with targeting ligands are considered to be the most effective strategies. In this study, novel dextran wrapped and peptide WSGPGVWGASVK (peptide-WSG) grafted USPIOs were meticulously prepared and systematically characterized. Firstly, dextran (Dex) cladded USPIOs (USPIOs@Dex) were synthesized with a well-designed co-precipitation procedure in which the biocompatible dextran played dual roles of grain inhibitor and cladding agent. After that, sodium citrate was applied to carboxylize the hydroxyls of the dextran molecules via an esterification reaction, and then tumor targeting peptide-WSG was grafted to the carboxyl groups by the EDC method. The XRD, TEM, and FTIR results showed that inverse spinel structure Fe(3)O(4) crystallites were nucleated and grown in aqueous solution, and the catenulate dextran molecules gradually bound on their surface, meanwhile the growth of grains was inhibited. The size of original crystallite grains was about 7 nm, but the mean size of USPIOs@Dex aggregates was 165.20 nm. After surface modification by sodium citrate and peptide-WSG with ultrasonic agitation, the size of the USPIOs@Dex-WSG aggregates was smaller (66.06 nm) because the hydrophilicity was improved, so USPIOs@Dex-WSG could evade being eliminated by RES more easily, and prolong residence time in blood circulation. The VSM and T(2)-weighted MRI results showed that USPIOs@Dex-WSG were superparamagnetic with a saturation magnetization of 44.65 emu g(−1), and with high transverse relaxivity as the R(2) relaxivity coefficient value was 229.70 mM(−1) s(−1). The results of MTT assays and the Prussian blue staining in vitro revealed that USPIOs@Dex-WSG exhibited nontoxicity for normal cells such as L929 and HUVECs, and were specifically targeted to the SKOV-3 cells. Thus, the novel dextran wrapped and WSG-peptide grafted USPIOs have potential to be applied as tumor active targeting contrast agents for MRI.
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spelling pubmed-90654002022-05-04 Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent Yin, Jie Yin, Guangfu Pu, Ximing Huang, Zhongbing Yao, Dajin RSC Adv Chemistry As desirable contrast agents for magnetic resonance imaging (MRI), ultrasmall superparamagnetic iron oxides (USPIOs) are required to exhibit both low cytotoxicity and specific targetability besides superparamagnetism to achieve better imaging contrast at lower dose, and cladding with biocompatible polymers and modification with targeting ligands are considered to be the most effective strategies. In this study, novel dextran wrapped and peptide WSGPGVWGASVK (peptide-WSG) grafted USPIOs were meticulously prepared and systematically characterized. Firstly, dextran (Dex) cladded USPIOs (USPIOs@Dex) were synthesized with a well-designed co-precipitation procedure in which the biocompatible dextran played dual roles of grain inhibitor and cladding agent. After that, sodium citrate was applied to carboxylize the hydroxyls of the dextran molecules via an esterification reaction, and then tumor targeting peptide-WSG was grafted to the carboxyl groups by the EDC method. The XRD, TEM, and FTIR results showed that inverse spinel structure Fe(3)O(4) crystallites were nucleated and grown in aqueous solution, and the catenulate dextran molecules gradually bound on their surface, meanwhile the growth of grains was inhibited. The size of original crystallite grains was about 7 nm, but the mean size of USPIOs@Dex aggregates was 165.20 nm. After surface modification by sodium citrate and peptide-WSG with ultrasonic agitation, the size of the USPIOs@Dex-WSG aggregates was smaller (66.06 nm) because the hydrophilicity was improved, so USPIOs@Dex-WSG could evade being eliminated by RES more easily, and prolong residence time in blood circulation. The VSM and T(2)-weighted MRI results showed that USPIOs@Dex-WSG were superparamagnetic with a saturation magnetization of 44.65 emu g(−1), and with high transverse relaxivity as the R(2) relaxivity coefficient value was 229.70 mM(−1) s(−1). The results of MTT assays and the Prussian blue staining in vitro revealed that USPIOs@Dex-WSG exhibited nontoxicity for normal cells such as L929 and HUVECs, and were specifically targeted to the SKOV-3 cells. Thus, the novel dextran wrapped and WSG-peptide grafted USPIOs have potential to be applied as tumor active targeting contrast agents for MRI. The Royal Society of Chemistry 2019-06-20 /pmc/articles/PMC9065400/ /pubmed/35519366 http://dx.doi.org/10.1039/c9ra02636c Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Yin, Jie
Yin, Guangfu
Pu, Ximing
Huang, Zhongbing
Yao, Dajin
Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent
title Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent
title_full Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent
title_fullStr Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent
title_full_unstemmed Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent
title_short Preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting MRI contrast agent
title_sort preparation and characterization of peptide modified ultrasmall superparamagnetic iron oxides used as tumor targeting mri contrast agent
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065400/
https://www.ncbi.nlm.nih.gov/pubmed/35519366
http://dx.doi.org/10.1039/c9ra02636c
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