Cancer Nanotechnology (May 2025)

Polyaniline-coated iron oxide nanoparticles reprogram macrophages and modulate the tumor microenvironment to inhibit breast cancer progression and metastasis

  • Camila Sales Nascimento,
  • Júlia Gallo Carvalho,
  • Naiara Clemente Tavares,
  • Anna Carolina Pinheiro Lage,
  • Marcelo Antônio Pascoal-Xavier,
  • Celso Pinto de Melo,
  • Érica Alessandra Rocha Alves,
  • Carlos Eduardo Calzavara-Silva

DOI
https://doi.org/10.1186/s12645-025-00323-4
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 25

Abstract

Read online

Abstract Background Breast cancer is a prevalent and complex disease with treatment limitations, including resistance, adverse side effects, and high recurrence rates. Tumor-associated macrophages (TAMs) are key players in breast cancer progression, with M2 TAMs promoting tumor growth and M1 TAMs inhibiting it. This study investigated the potential of polyaniline-coated iron oxide nanoparticles (Pani/γ-Fe2O3 NPs) to modulate the tumor microenvironment through macrophage reprogramming and broader immune effects in vitro and in vivo, offering a basis for innovative cancer immunotherapy approaches. Results In the in vitro study Pani/y-Fe2O3 demonstrated the ability to induce changes in the tumor microenvironment to an anti-tumoral profile leading to tumor cell apoptosis, enhance the production of pro-inflammatory cytokines (IL-12p70, TNF-α, and IL-6), and elevate hydrogen peroxide levels. In the 4T1 BALB/c model of metastatic breast cancer, Pani/γ-Fe2O3 treatment resulted in a 50% reduction in both tumor weight and volume. Tumor analysis showed a decrease in mitotic cell counts, an increase in natural killer (NK) cells and CD86+ macrophages, a reduction in neutrophil proportions, and suppression of MCP-1 cytokine production. Additionally, Pani/γ-Fe2O3 effectively inhibited 4T1 cell metastasis to the lungs. Conclusions This study highlights the potential of Pani/y-Fe2O3 as an immunostimulatory agent, capable of driving macrophage polarization and modulating the tumor microenvironment, inhibiting tumor progression and metastasis. These findings provide promising insights into the use of iron oxide nanoparticles as a novel tool for breast cancer immunotherapy.

Keywords