Development of Immune-Regulatory Pseudo-Protein-Coated Iron Oxide Nanoparticles for Enhanced Treatment of Triple-Negative Breast Tumor

TL;DR

Researchers developed iron oxide nanoparticles coated with a special polymer to boost immune response against triple-negative breast cancer.

Contribution

A novel polymer-coated nanoparticle strategy to regulate macrophages and enhance anti-tumor immunity in triple-negative breast cancer.

Findings

APU-R848-IONPs reduced the M2/M1 macrophage ratio by 51% in tumor models.

The treatment increased cytotoxic T cells and tumoricidal cytokine production.

APU-R848-IONPs showed 3.2-fold higher anti-tumor efficacy compared to controls.

Abstract

Triple-negative breast cancer (TNBC) frequently evades immune recognition and elimination, resulting in an immunosuppressive microenvironment. The phagocytic activity of tumor-associated macrophages underscores the development of nanomaterials as a promising strategy to target these macrophages and modulate their polarization, thereby advancing immunotherapy against TNBC. This research developed functional polymers that are complexed with therapeutic molecules as a coating strategy for iron oxide nanoparticles. An arginine-based poly (ester urea urethane) polymer complexed with a macrophage-polarizing molecule (APU-R848) could provide a synergistic effect with iron oxide nanoparticles (IONPs) to stimulate the M1-polarization of macrophages at the tumor site, resulting in a versatile nano-platform for immune regulation of TNBC. In the 4T1 in vivo breast tumor model, the APU-R848-IONPs demonstrated an improved intratumoral biodistribution compared to IONPs without a polymer coating. APU-R848-IONPs significantly reversed the immune-suppressive tumor environment by reducing the M2/M1 macrophage phenotype ratio by 51%, associated with an elevated population of cytotoxic T cells and a significantly enhanced production of tumoricidal cytokines. The activated immune response induced by APU-R848-IONP resulted in a significant anti-tumor effect, demonstrating an efficacy that was more than 3.2-fold more efficient compared to the controls. These immune-regulatory pseudo-protein-coated iron oxide nanoparticles represent an effective nano-strategy for macrophages’ regulation and the activation of anti-tumor immunity, providing a new treatment modality for triple-negative breast cancer.

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