Multiple Presentation of Scfv800E6 on Silica Nanospheres Enhances Targeting Efficiency Toward HER-2 Receptor in Breast Cancer Cells

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• 作者：Serena Mazzucchelli ; Paolo Verderio ; Silvia Sommaruga ; Miriam Colombo ; Agnese Salvad猫 ; Fabio Corsi ; Patrizia Galeffi ; Paolo Tortora ; Davide Prosperi
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：November 16, 2011
• 年：2011
• 卷：22
• 期：11
• 页码：2296-2303
• 全文大小：360K
• 年卷期：v.22,no.11(November 16, 2011)
• ISSN：1520-4812

文摘

Spherical silica nanoparticles (SNP) have been synthesized and functionalized with anti-HER-2 scFv800E6 antibody by both localized histidine-tag recognition, leading to an oriented protein ligation, and glutaraldehyde cross-linking, exploiting a statistical reactivity of lysine amine groups in the primary sequence of the molecule. The targeting efficiency of nanocomplexes in comparison with free scFv was evaluated by flow cytometry using a HER-2 antigen-positive MCF-7 breast cancer cell line, exhibiting a 4-fold increase in scFv binding efficacy, close to the affinity of intact anti-HER-2 monoclonal antibody, which suggests the effectiveness of presenting multiple scFv molecules on nanoparticles in improving antigen recognition. Unexpectedly, the conjugation method did not affect the binding efficacy of scFv, suggesting a structural role of lysines in the scFv molecule. Confocal laser scanning microscopy confirmed the binding of nanocomplexes to HER-2 and also provided evidence of their localization at the cell surface.