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Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent
INTRODUCTION: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl(4)) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl(3) * 6 H(2)O) to form DOX IN-Gd-AuN...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982711/ https://www.ncbi.nlm.nih.gov/pubmed/33762822 http://dx.doi.org/10.2147/IJN.S295809 |
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author | Khan, Memona Boumati, Sarah Arib, Celia Thierno Diallo, Amadou Djaker, Nadia Doan, Bich-thuy Spadavecchia, Jolanda |
author_facet | Khan, Memona Boumati, Sarah Arib, Celia Thierno Diallo, Amadou Djaker, Nadia Doan, Bich-thuy Spadavecchia, Jolanda |
author_sort | Khan, Memona |
collection | PubMed |
description | INTRODUCTION: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl(4)) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl(3) * 6 H(2)O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption. MATERIAL AND METHOD: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation. RESULTS: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r(1) relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues. CONCLUSION: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T(1) features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications. |
format | Online Article Text |
id | pubmed-7982711 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-79827112021-03-23 Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent Khan, Memona Boumati, Sarah Arib, Celia Thierno Diallo, Amadou Djaker, Nadia Doan, Bich-thuy Spadavecchia, Jolanda Int J Nanomedicine Original Research INTRODUCTION: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl(4)) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl(3) * 6 H(2)O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption. MATERIAL AND METHOD: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation. RESULTS: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r(1) relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues. CONCLUSION: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T(1) features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications. Dove 2021-03-17 /pmc/articles/PMC7982711/ /pubmed/33762822 http://dx.doi.org/10.2147/IJN.S295809 Text en © 2021 Khan et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Khan, Memona Boumati, Sarah Arib, Celia Thierno Diallo, Amadou Djaker, Nadia Doan, Bich-thuy Spadavecchia, Jolanda Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent |
title | Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent |
title_full | Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent |
title_fullStr | Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent |
title_full_unstemmed | Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent |
title_short | Doxorubicin (DOX) Gadolinium–Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent |
title_sort | doxorubicin (dox) gadolinium–gold-complex: a new way to tune hybrid nanorods as theranostic agent |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982711/ https://www.ncbi.nlm.nih.gov/pubmed/33762822 http://dx.doi.org/10.2147/IJN.S295809 |
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