In vivo delineation of glioblastoma by targeting tumor-associated macrophages with near-infrared fluorescent silica coated iron oxide nanoparticles in orthotopic xenografts for surgical guidance

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and lethal type of human brain cancer. Surgery is a current gold standard for GBM treatment but the complete surgical resection of GBM is almost impossible due to their diffusive characteristics into surrounded normal brain tissues. There is an urgent need to develop a sensitive imaging tool for accurate delineation of GBM in the operating room to guide surgeons. Here we illustrate the feasibility of using near-infrared fluorescent silica coated iron oxide nanoparticles (NF-SIONs) with high water dispersion capacity and strong fluorescence stability for intraoperative imaging of GBM by targeting tumor-associated macrophages. Abundant macrophage infiltration is a key feature of GBM margins and it is well associated with poor prognosis. We synthesized NF-SIONs of about 37 nm to maximize endocytosis activity for macrophage uptake. The NF-SIONs selectively visualized tumor-associated macrophage populations by in vitro live-cell imaging and in vivo fluorescence imaging. In the orthotopic GBM xenograft models, the NF-SIONs could successfully penetrate blood-brain barrier and delineated tumor burden specifically. Taken together, this study showcased the potential applications in GBM treatment for improved intraoperative staging and more radical surgery as well as dual modality benefit in order to circumvent previous clinical failure.