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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...

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Autores principales: Song, Lina, Zhang, Wei, Chen, Hong, Zhang, Xizhi, Wu, Haoan, Ma, Ming, Wang, Zhongqiu, Gu, Ning, Zhang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2019
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.
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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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