Targeting Glioblastoma-Associated Macrophages for Photodynamic Therapy Using AGuIX^®-Design Nanoparticles

Area of Science:

• Oncology
• Nanomedicine
• Immunology

Background:

• Glioblastoma (GBM) is a challenging brain cancer.
• Photodynamic therapy (PDT) is a promising complementary treatment for GBM.
• Neuropilin-1 (NRP-1) expression is linked to GBM progression and M2 macrophage infiltration.

Purpose of the Study:

• To investigate how macrophage NRP-1 expression affects the uptake of AGuIX-design nanoparticles.
• To determine the influence of GBM cell secretome post-PDT on macrophage polarization (M1/M2).

Main Methods:

• THP-1 human monocytes were polarized into M1 and M2 macrophages.
• Macrophage polarization was confirmed via morphology, cell impedance, and gene expression (TNFα, CXCL10, CD-80, CD-163, CD-206, CCL22).
• Functionalized AGuIX-design nanoparticles targeting NRP-1 were used.

Main Results:

• M2 macrophages with NRP-1 over-expression showed a three-fold increase in nanoparticle uptake compared to M1 macrophages.
• GBM cell secretome post-PDT induced M1 polarization, evidenced by increased TNFα transcript levels.
• A correlation between post-PDT efficacy and inflammatory effects involving macrophages was observed.

Conclusions:

• Macrophage phenotype and NRP-1 expression significantly impact nanoparticle uptake in GBM.
• Targeting NRP-1 on M2 macrophages could enhance PDT efficacy.
• Macrophages play a crucial role in the inflammatory response within the GBM tumor microenvironment post-PDT.