NaGdF4-based magnetic resonance nanoprobes for qualitative inflammation imaging in glioma: Hot or cold?

Abstract

The ‘cold’ or ‘hot’ inflammatory status of glioblastoma (GBM) is closely related to the responsiveness of immunotherapy. Tumor-associated macrophages (TAMs) are the most abundant tumor infiltrating immune cells in the tumor microenvironment (TME) of GBM, which can be classified as pro- (M1-like) and anti-inflammatory (M2-like) phenotype. M1-like TAMs present in large amount in ‘hot’ TME and indicate better immunotherapeutic outcome, which secrete myeloperoxidase (MPO) to promote inflammation in host defense. Herein, magnetic resonance imaging (MRI) based Tyr-ANG-NaGdF4 nanoprobes, named as TAGs, with surface modification of ANG to target glioma and phenolic hydroxyl to sense MPO were developed, aiming to noninvasively visualize the ‘hot’ or ‘cold’ TME inflammatory status of GBM based on MRI. Rat C6 gliomas, which were histologically confirmed as MPO-enriched ‘hot’ TME, showed patchy hypointense T1 signal within the tumor after intravenous administration of TAGs, ascribing to the MPO responsive assembly of the nanoprobes which led to the T1 signal reverse. On the contrary, mouse GL261 gliomas, which was histologically confirmed as MPO-rare ‘cold’ TME, presented moderate hyperintensity in T1-weighted MRI. Therefore, the MPO responsive nanoprobes present potential means to monitor the TME inflammatory status for GBM patients thus guide clinical treatment.