癌症研究
癌症
氧化铁纳米粒子
纳米颗粒
乳腺癌
乳腺肿瘤
材料科学
肺癌
氧化铁
纳米技术
医学
化学
内科学
冶金
作者
Preethi Korangath,Lü Jin,Chun Yang,S. B. Healy,Xin Guo,Suqi Ke,Cordula Grüttner,Chen Hu,Kathleen Gabrielson,Jeremy B. Foote,Robert B. Clarke,Robert Ivkov
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-04-02
标识
DOI:10.1021/acsnano.3c12064
摘要
Systemic exposure to starch-coated iron oxide nanoparticles (IONPs) can stimulate antitumor T cell responses, even when little IONP is retained within the tumor. Here, we demonstrate in mouse models of metastatic breast cancer that IONPs can alter the host immune landscape, leading to systemic immune-mediated disease suppression. We report that a single intravenous injection of IONPs can inhibit primary tumor growth, suppress metastases, and extend survival. Gene expression analysis revealed the activation of Toll-like receptor (TLR) pathways involving signaling via Toll/Interleukin-1 receptor domain-containing adaptor-inducing IFN-β (TRIF), a TLR pathway adaptor protein. Requisite participation of TRIF in suppressing tumor progression was demonstrated with histopathologic evidence of upregulated IFN-regulatory factor 3 (IRF3), a downstream protein, and confirmed in a TRIF knockout syngeneic mouse model of metastatic breast cancer. Neither starch-coated polystyrene nanoparticles lacking iron, nor iron-containing dextran-coated parenteral iron replacement agent, induced significant antitumor effects, suggesting a dependence on the type of IONP formulation. Analysis of multiple independent clinical databases supports a hypothesis that upregulation of TLR3 and IRF3 correlates with increased overall survival among breast cancer patients. Taken together, these data support a compelling rationale to re-examine IONP formulations as harboring anticancer immune (nano)adjuvant properties to generate a therapeutic benefit without requiring uptake by cancer cells.
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