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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Detalles Bibliográficos
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:
Original Research
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
Descripción
Sumario: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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