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

Fiche publication

Date publication

mars 2023

Journal

Pharmaceutics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel , Dr FROCHOT Céline , Dr THOMAS Noémie , Dr DAOUK Joël

Tous les auteurs :
Lerouge L, Gries M, Chateau A, Daouk J, Lux F, Rocchi P, Cedervall J, Olsson AK, Tillement O, Frochot C, Acherar S, Thomas N, Barberi-Heyob M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36986856

Résumé

Glioblastoma (GBM) is the most difficult brain cancer to treat, and photodynamic therapy (PDT) is emerging as a complementary approach to improve tumor eradication. Neuropilin-1 (NRP-1) protein expression plays a critical role in GBM progression and immune response. Moreover, various clinical databases highlight a relationship between NRP-1 and M2 macrophage infiltration. In order to induce a photodynamic effect, multifunctional AGuIX-design nanoparticles were used in combination with a magnetic resonance imaging (MRI) contrast agent, as well as a porphyrin as the photosensitizer molecule and KDKPPR peptide ligand for targeting the NRP-1 receptor. The main objective of this study was to characterize the impact of macrophage NRP-1 protein expression on the uptake of functionalized AGuIX-design nanoparticles in vitro and to describe the influence of GBM cell secretome post-PDT on the polarization of macrophages into M1 or M2 phenotypes. By using THP-1 human monocytes, successful polarization into the macrophage phenotypes was argued via specific morphological traits, discriminant nucleocytoplasmic ratio values, and different adhesion abilities based on real-time cell impedance measurements. In addition, macrophage polarization was confirmed via the transcript-level expression of TNFα, CXCL10, CD-80, CD-163, CD-206, and CCL22 markers. In relation to NRP-1 protein over-expression, we demonstrated a three-fold increase in functionalized nanoparticle uptake for the M2 macrophages compared to the M1 phenotype. The secretome of the post-PDT GBM cells led to nearly a three-fold increase in the over-expression of TNFα transcripts, confirming the polarization to the M1 phenotype. The in vivo relationship between post-PDT efficiency and the inflammatory effects points to the extensive involvement of macrophages in the tumor zone.