Recombinant Interleukin-1 Receptor Antagonist Conjugated to Superparamagnetic Iron Oxide Nanoparticles for Theranostic Targeting of

Cerebral edema commonly accompanies brain tumors and contributes to neurologic symptoms. The role of the interleukin-1 receptor antagonist conjugated to superparamagnetic iron oxide nanoparticles (SPION–IL-1Ra) was assessed to analyze its anti-edemal effect and its possible application as a negative contrast enhancing agent for magnetic resonance imaging (MRI). Rats with intracranial C6 glioma were intravenously administered at various concentrations of IL-1Ra or SPION–IL-1Ra. Brain peritumoral edema following treatment with receptor antagonist was assessed with high-field MRI. IL-1Ra administered at later stages of tumor progression significantly reduced peritumoral edema (as measured by MRI) and prolonged two-fold the life span of comorbid animals in a dosedependent manner in comparison to control and corticosteroid-treated animals (P b .001). Synthesized SPION–IL-1Ra conjugateshadthepropertiesofnegativecontrastagentwithhighcoefficientsofrelaxationefficiency.Invitrostudiesof SPION–IL-1Ra nanoparticles demonstrated high intracellular incorporation and absence of toxic influence on C6 cells andlymphocyteviabilityandproliferation.Retentionofthenanoparticles inthetumorresulted inenhancedhypotensive T2-weighted images of glioma, proving the application of the conjugates as negative magnetic resonance contrast agents. Moreover, nanoparticles reduced the peritumoral edema confirming the therapeutic potency of synthesized conjugates. SPION–IL-1Ra nanoparticles have an anti-edemal effect when administered through a clinically relevant route in animals with glioma. The SPION–IL-1Ra could be a candidate for theranostic approach in neuro-oncology both for diagnosis of brain tumors and management of peritumoral edema.