Neutrophil Nanodecoys Inhibit Tumor Metastasis by Blocking the Interaction between Tumor Cells and Neutrophils

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Cancer metastasis is a primary cause of cancer-related mortality.
• Neutrophils play a critical role in facilitating cancer metastasis through complex interactions with tumor cells.
• Targeting these neutrophil-tumor cell interactions presents a therapeutic opportunity.

Purpose of the Study:

• To develop activated neutrophil membrane-coated nanoparticles (aNEM NPs) as nanodecoys.
• To investigate the efficacy of aNEM NPs in blocking neutrophil-mediated cancer metastasis.
• To evaluate the potential of aNEM NPs as a nanomedicine for preventing or treating metastasis.

Main Methods:

• Fabrication of aNEM NPs by cloaking poly(lactic acid) nanoparticles with activated neutrophil membranes.
• In vitro and in vivo studies to assess the interference of aNEM NPs with neutrophil recruitment, adhesion, and cluster formation.
• Evaluation of aNEM NP efficacy in reducing breast cancer metastasis in a 4T1-bearing mouse model.

Main Results:

• aNEM NPs successfully inherited functional proteins from activated neutrophils.
• aNEM NPs demonstrated the ability to interfere with neutrophil recruitment to tumors and premetastatic niches.
• Inhibition of neutrophil adhesion to tumor vascular endothelium and circulating tumor cells (CTCs) was observed.
• Disruption of CTC-neutrophil cluster formation occurred both in vitro and in vivo.
• Significant reduction in breast cancer metastasis to various organs was achieved in mice treated with aNEM NPs.

Conclusions:

• aNEM NPs effectively act as neutrophil nanodecoys to inhibit cancer metastasis.
• The developed nanomedicine shows promise in preventing or treating metastasis by targeting neutrophil-mediated processes.
• This approach offers a novel strategy for combating cancer spread and improving patient outcomes.