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Apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with CD20 overexpression
BACKGROUND: Cancer targeting nanoprobes with precisely designed physicochemical properties may show enhanced pharmacological targeting and therapeutic efficacy. As a widely used commercialized antibody, rituximab has been in clinical use for three decades and has lengthened or even saved thousands o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363495/ https://www.ncbi.nlm.nih.gov/pubmed/30787607 http://dx.doi.org/10.2147/IJN.S185458 |
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author | Song, Lina Zhang, Wei Chen, Hong Zhang, Xizhi Wu, Haoan Ma, Ming Wang, Zhongqiu Gu, Ning Zhang, Yu |
author_facet | Song, Lina Zhang, Wei Chen, Hong Zhang, Xizhi Wu, Haoan Ma, Ming Wang, Zhongqiu Gu, Ning Zhang, Yu |
author_sort | Song, Lina |
collection | PubMed |
description | BACKGROUND: Cancer targeting nanoprobes with precisely designed physicochemical properties may show enhanced pharmacological targeting and therapeutic efficacy. As a widely used commercialized antibody, rituximab has been in clinical use for three decades and has lengthened or even saved thousands of lives. However, many people cannot benefit from rituximab treatment because of drug resistance or side effects. METHODS: In this study, a 13-nm rituximab-conjugated magnetic nanoparticle was developed as a therapeutic nanoprobe targeting CD20 overexpressing malignant lymphoma cells to enhance the treatment effects of rituximab. The magnetic cores (2,3-dimercaptosuccinicacid modified Fe(3)O(4) nanoparticles, Fe(3)O(4)@DMSA) of the nanoprobes with an average diameter of 6.5 nm were synthesized using a co-precipitation method. Rituximab was then conjugated on the surface of Fe(3)O(4)@DMSA using a cross-linking agent (carbodiimide/N-hydroxysulfosuccinimide sodium salt). Based on theoretical calculations, approximately one antibody was coupled with one nanoparticle, excluding the multivalent antibody effect. RESULTS: Cell targeting experiments and magnetic resonance (MR) signal and T2 measurements showed that the Fe(3)O(4)@DMSA@Ab nanoprobes have specific binding affinity for CD20-positive cells. Compared to rituximab and Fe(3)O(4)@DMSA, Fe(3)O(4)@DMSA@Ab nanoprobes significantly reduced cell viability and promoted Raji cell apoptosis. Initiating events of apoptosis, including increased intracellular calcium and reactive oxygen species, were observed in nanoprobe-treated Raji cells. Nanoprobe-treated Raji cells also showed the most drastic decrease in mitochondrial membrane potential and Bcl-2 expression, compared to rituximab and Fe(3)O(4)@DMSA-treated Raji cells. CONCLUSION: These results indicate that Fe(3)O(4)@DMSA@Ab nanoprobes have the potential to serve as MRI tracers and therapeutic agents for CD20-positive cells. |
format | Online Article Text |
id | pubmed-6363495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63634952019-02-20 Apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with CD20 overexpression Song, Lina Zhang, Wei Chen, Hong Zhang, Xizhi Wu, Haoan Ma, Ming Wang, Zhongqiu Gu, Ning Zhang, Yu Int J Nanomedicine Original Research BACKGROUND: Cancer targeting nanoprobes with precisely designed physicochemical properties may show enhanced pharmacological targeting and therapeutic efficacy. As a widely used commercialized antibody, rituximab has been in clinical use for three decades and has lengthened or even saved thousands of lives. However, many people cannot benefit from rituximab treatment because of drug resistance or side effects. METHODS: In this study, a 13-nm rituximab-conjugated magnetic nanoparticle was developed as a therapeutic nanoprobe targeting CD20 overexpressing malignant lymphoma cells to enhance the treatment effects of rituximab. The magnetic cores (2,3-dimercaptosuccinicacid modified Fe(3)O(4) nanoparticles, Fe(3)O(4)@DMSA) of the nanoprobes with an average diameter of 6.5 nm were synthesized using a co-precipitation method. Rituximab was then conjugated on the surface of Fe(3)O(4)@DMSA using a cross-linking agent (carbodiimide/N-hydroxysulfosuccinimide sodium salt). Based on theoretical calculations, approximately one antibody was coupled with one nanoparticle, excluding the multivalent antibody effect. RESULTS: Cell targeting experiments and magnetic resonance (MR) signal and T2 measurements showed that the Fe(3)O(4)@DMSA@Ab nanoprobes have specific binding affinity for CD20-positive cells. Compared to rituximab and Fe(3)O(4)@DMSA, Fe(3)O(4)@DMSA@Ab nanoprobes significantly reduced cell viability and promoted Raji cell apoptosis. Initiating events of apoptosis, including increased intracellular calcium and reactive oxygen species, were observed in nanoprobe-treated Raji cells. Nanoprobe-treated Raji cells also showed the most drastic decrease in mitochondrial membrane potential and Bcl-2 expression, compared to rituximab and Fe(3)O(4)@DMSA-treated Raji cells. CONCLUSION: These results indicate that Fe(3)O(4)@DMSA@Ab nanoprobes have the potential to serve as MRI tracers and therapeutic agents for CD20-positive cells. Dove Medical Press 2019-02-01 /pmc/articles/PMC6363495/ /pubmed/30787607 http://dx.doi.org/10.2147/IJN.S185458 Text en © 2019 Song et al. 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. |
spellingShingle | Original Research Song, Lina Zhang, Wei Chen, Hong Zhang, Xizhi Wu, Haoan Ma, Ming Wang, Zhongqiu Gu, Ning Zhang, Yu Apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with CD20 overexpression |
title | Apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with CD20 overexpression |
title_full | Apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with CD20 overexpression |
title_fullStr | Apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with CD20 overexpression |
title_full_unstemmed | Apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with CD20 overexpression |
title_short | Apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with CD20 overexpression |
title_sort | apoptosis-promoting effect of rituximab-conjugated magnetic nanoprobes on malignant lymphoma cells with cd20 overexpression |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363495/ https://www.ncbi.nlm.nih.gov/pubmed/30787607 http://dx.doi.org/10.2147/IJN.S185458 |
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