Kempe, E. G. | Search bioRxiv

bioRxiv2025

Enhanced Detection of Glioblastoma Vasculature with Superparamagnetic Iron Oxide Nanoparticles and MRI

Detecting glioblastoma infiltration in the brain is challenging due to limited MRI contrast beyond the enhancing tumour core. This study aims to investigate the potential of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents for improved detection of diffuse brain cancer. We examine the distribution and pharmacokinetics of SPIONs in glioblastoma models with intact and disrupted blood-brain barriers. Using MRI, we imaged RN1-luc and U87MG mice injected with Gadovist and SPIONs, observing differences in blood-brain barrier permeability. Peripheral imaging showed strong uptake of nanoparticles in the liver and spleen, while vascular and renal signals were transient. Susceptibility gradient mapping enabled positive nanoparticle contrast within tumours and provided additional information on tumour angiogenesis. This approach offers a novel method for detecting diffuse brain cancer. Our findings demonstrate that SPIONs enhance glioblastoma detection beyond conventional MRI, providing insights into tumour angiogenesis and opening new avenues for early diagnosis and targeted treatment strategies.

cancer biology↗

bioRxiv2025

Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma

Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug- tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screen, we identified that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy- induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, resulted in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings demonstrate a previously unknown role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells.

cancer biology↗