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卷曲蛋白 7 抗体功能化纳米壳允许多价结合用于三阴性乳腺癌细胞中的 Wnt 信号抑制。

Frizzled7 Antibody-Functionalized Nanoshells Enable Multivalent Binding for Wnt Signaling Inhibition in Triple Negative Breast Cancer Cells.

机构信息

Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, 150 Academy Street, Newark, DE, 19716, USA.

Department of Materials Science and Engineering, University of Delaware, Newark, DE, 19716, USA.

出版信息

Small. 2017 Jul;13(26). doi: 10.1002/smll.201700544. Epub 2017 May 22.


DOI:10.1002/smll.201700544
PMID:28544579
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5545881/
Abstract

Antibodies that antagonize cell signaling pathways specific to their targeted receptor are invaluable tools to study and treat malignancies, but their utility is limited by high production costs and treatment dosages. Researchers have shown that antibodies conjugated to nanoparticles display increased affinity for their target relative to freely delivered antibodies due to multivalency, and this study investigates how this multivalency can enable antibody-nanoparticle conjugates to inhibit oncogenic cell signaling more effectively than freely delivered antibodies. This effect was evaluated using triple negative breast cancer (TNBC) cells that are characterized by hyperactive Wnt signaling mediated through overexpressed Frizzled7 (FZD7) transmembrane receptors. Through analysis of the expression of β-catenin and Axin2, two downstream targets in the Wnt pathway, the results demonstrate that FZD7 antibody-nanoshell conjugates (FZD7-NS) are drastically more effective at inhibiting Wnt signaling in TNBC cells than freely delivered FZD7 antibodies. Additionally, cells treated with FZD7-NS, but not cells treated with freely delivered FZD7 antibodies, have decreased viability, indicating the therapeutic potential of this technology. The results demonstrate that antibody-functionalized nanoparticles can exploit multivalency for improved signal cascade interference over free antibodies, and this may ultimately permit lower antibody dosages to be administered to study signaling pathways or to manage diseases.

摘要

拮抗特定于其靶受体的细胞信号通路的抗体是研究和治疗恶性肿瘤的宝贵工具,但由于高生产成本和治疗剂量,其用途受到限制。研究人员已经表明,与自由递呈的抗体相比,连接到纳米颗粒上的抗体由于多价性而显示出对其靶标的更高亲和力,本研究调查了这种多价性如何使抗体-纳米颗粒缀合物比自由递呈的抗体更有效地抑制致癌细胞信号。使用三阴性乳腺癌 (TNBC) 细胞评估了这种效应,这些细胞的特征是通过过度表达的 Frizzled7 (FZD7) 跨膜受体介导的 Wnt 信号过度活跃。通过分析 Wnt 通路的两个下游靶标 β-连环蛋白和 Axin2 的表达,结果表明,FZD7 抗体-纳米壳缀合物 (FZD7-NS) 比自由递呈的 FZD7 抗体更有效地抑制 TNBC 细胞中的 Wnt 信号。此外,用 FZD7-NS 处理的细胞而非用自由递呈的 FZD7 抗体处理的细胞活力降低,表明该技术具有治疗潜力。结果表明,抗体功能化的纳米颗粒可以利用多价性来改善信号级联干扰,而这最终可能允许降低抗体剂量以研究信号通路或管理疾病。

相似文献

[1]
Frizzled7 Antibody-Functionalized Nanoshells Enable Multivalent Binding for Wnt Signaling Inhibition in Triple Negative Breast Cancer Cells.

Small. 2017-5-22

[2]
A novel recombinant human Frizzled-7 protein exhibits anti-tumor activity against triple negative breast cancer via abating Wnt/β-catenin pathway.

Int J Biochem Cell Biol. 2018-8-7

[3]
Inhibition of Wnt signaling by Frizzled7 antibody-coated nanoshells sensitizes triple-negative breast cancer cells to the autophagy regulator chloroquine.

Nano Res. 2020-6

[4]
A novel humanized Frizzled-7-targeting antibody enhances antitumor effects of Bevacizumab against triple-negative breast cancer via blocking Wnt/β-catenin signaling pathway.

J Exp Clin Cancer Res. 2021-1-12

[5]
Antibody and siRNA Nanocarriers to Suppress Wnt Signaling, Tumor Growth, and Lung Metastasis in Triple-Negative Breast Cancer.

Adv Ther (Weinh). 2024-6

[6]
Cell growth inhibition and apoptosis in breast cancer cells induced by anti-FZD7 scFvs: involvement of bioinformatics-based design of novel epitopes.

Breast Cancer Res Treat. 2018-2-6

[7]
Frizzled7 as an emerging target for cancer therapy.

Cell Signal. 2011-12-13

[8]
Frizzled7 Promotes Epithelial-to-mesenchymal Transition and Stemness Via Activating Canonical Wnt/β-catenin Pathway in Gastric Cancer.

Int J Biol Sci. 2018-2-12

[9]
FZD7-Targeted Nanoparticles to Enhance Doxorubicin Treatment of Triple-Negative Breast Cancer.

ACS Omega. 2024-3-16

[10]
FZD7 has a critical role in cell proliferation in triple negative breast cancer.

Oncogene. 2011-5-2

引用本文的文献

[1]
Frizzled-7-targeting antibody-derived bifunctional protein retargets NK cells against triple-negative breast cancer cells via MICA-NKG2D axis.

J Immunother Cancer. 2025-2-27

[2]
Antibody/siRNA Nanocarriers Against Wnt Signaling Suppress Oncogenic and Stem-Like Behavior in Triple-Negative Breast Cancer Cells.

J Biomed Mater Res A. 2025-1

[3]
Conjugation of Antibodies and siRNA Duplexes to Polymer Nanoparticles via Maleimide-Thiol Chemistry.

ACS Omega. 2024-11-18

[4]
Antibody and siRNA Nanocarriers to Suppress Wnt Signaling, Tumor Growth, and Lung Metastasis in Triple-Negative Breast Cancer.

Adv Ther (Weinh). 2024-6

[5]
Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Acta Pharmacol Sin. 2024-8

[6]
FZD7-Targeted Nanoparticles to Enhance Doxorubicin Treatment of Triple-Negative Breast Cancer.

ACS Omega. 2024-3-16

[7]
Membrane-Cloaked Nanoparticles for RNA Interference of β-Catenin in Triple-Negative Breast Cancer.

ACS Biomater Sci Eng. 2024-3-11

[8]
E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells.

ACS Appl Nano Mater. 2023-1-27

[9]
A novel retinoic acid drug, EYE-502, inhibits choroidal neovascularization by targeting endothelial cells and pericytes.

Sci Rep. 2023-6-27

[10]
Multivalent Ligand-Nanoparticle Conjugates Amplify Reactive Oxygen Species Second Messenger Generation and Enhance Epidermal Growth Factor Receptor Phosphorylation.

Bioconjug Chem. 2022-9-21

本文引用的文献

[1]
Effect of the Protein Corona on Antibody-Antigen Binding in Nanoparticle Sandwich Immunoassays.

Bioconjug Chem. 2017-1-18

[2]
Enhanced Human Epidermal Growth Factor Receptor 2 Degradation in Breast Cancer Cells by Lysosome-Targeting Gold Nanoconstructs.

ACS Nano. 2015-10-27

[3]
Initial Evaluation of the Safety of Nanoshell-Directed Photothermal Therapy in the Treatment of Prostate Disease.

Int J Toxicol. 2016

[4]
Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.

PLoS One. 2015-4-7

[5]
miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma.

Genes Dev. 2015-4-1

[6]
Inhibiting metastatic breast cancer cell migration via the synergy of targeted, pH-triggered siRNA delivery and chemokine axis blockade.

Mol Pharm. 2014-3-3

[7]
Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma.

Sci Transl Med. 2013-10-30

[8]
Antibody therapeutics in cancer.

Science. 2013-9-13

[9]
Triple-negative breast cancer: new perspectives for novel therapies.

Med Oncol. 2013-7-4

[10]
Big signals from small particles: regulation of cell signaling pathways by nanoparticles.

Chem Rev. 2013-5-8

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