Nanoparticulate Cationic Poly(amino acid)s Block Cancer Metastases by Destructing Neutrophil Extracellular Traps

Area of Science:

• Oncology
• Biomaterials Science
• Nanotechnology

Background:

• Cancer metastasis, resistant to therapies, is a leading cause of mortality.
• Neutrophil extracellular traps (NETs) and their cell-free DNA are implicated in promoting distant cancer spread.
• NET-DNA acts as a chemokine, binding to cancer cell transmembrane protein CCDC25 to drive migration.

Purpose of the Study:

• To develop novel poly(aspartic acid)-based cationic materials (cANP) to inhibit NET-DNA-mediated cancer cell metastasis.
• To investigate the efficacy of cANP in blocking the interaction between NET-DNA and CCDC25.
• To evaluate the therapeutic potential and safety of cANP in preclinical models of cancer metastasis.

Main Methods:

• Synthesis and characterization of poly(aspartic acid) derivatives (cANP).
• In vitro assays to assess the inhibition of NET-DNA and CCDC25 interaction.
• In vivo studies in mice and human metastatic models to evaluate the anti-metastatic efficacy and toxicity of cANP.

Main Results:

• cANP effectively interfered with the NET-DNA and CCDC25 interaction, inhibiting cancer cell migration.
• Nanoparticulate cANP demonstrated strong DNA binding and liver retention, reducing hepatic NET-DNA infiltration.
• Significant suppression of cancer metastases was observed in mice and human metastatic models treated with cANP.
• cANP exhibited no discernible toxicity to animal organs during treatment.

Conclusions:

• Poly(aspartic acid)-based cationic materials offer a promising strategy to combat cancer metastasis.
• Targeting the NET-DNA-CCDC25 interaction presents a novel therapeutic approach for metastatic cancer.
• cANP demonstrates significant anti-metastatic potential with a favorable safety profile, suggesting clinical applicability.