Engineering Controlled Peritumoral Inflammation to Constrain Brain Tumor Growth

Treatment of brain tumors presents an unmet clinical need, partly due to the migratory and invasive nature of tumor cells. Traumatic injury in the brain inflames and activates resident glial cells culminating in reactive gliosis that typically "walls‐off" the injury site. Here, the hypothesis is tested that activating and inflaming cells surrounding brain tumors result in the walling‐off and containment of invasive brain tumors.

Abstract

Brain tumors remain a great clinical challenge, in part due to their capacity to invade into eloquent, inoperable regions of the brain. In contrast, inflammation in the central nervous system (CNS) due to injuries activates microglia and astrocytes culminating in an astroglial scar that typically "walls‐off" the injury site. Here, the hypothesis is tested that targeting peritumoral cells surrounding tumors to activate them via an inflammatory stimulus that recapitulates the sequelae of a traumatic CNS injury, could generate an environment that would wall‐off and contain invasive tumors in the brain. Gold nanoparticles coated with inflammatory polypeptides to target stromal cells in close vicinity to glioblastoma (GBM) tumors, in order to activate these cells and stimulate stromal CNS inflammation, are engineered. It is reported that this approach significantly contains tumors in rodent models of GBM relative to control treatments (reduction in tumor volume by over 300% in comparison to controls), by the activation of the innate and adaptive immune response, and by triggering pathways related to cell clustering. Overall, this report outlines an approach to contain invasive tumors that can complement adjuvant interventions for invasive GBM such as radiation and chemotherapy.

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