Nose-to-Glioblastoma Axonal Transport of Manganese Ferrite Nanoparticles under the Influence of Olfactory Stimulation

Abstract

Nanotechnology-based approaches are increasingly recognized in cancer biology owing to their substantial impact on various tumor cells. Nanoparticles (NPs) can serve as carriers of nanoscale drug cargos and traverse neuronal cell membranes within the nasal cavity, thereby providing an effective means to bypass the blood–brain barrier, which otherwise limits the delivery of therapeutic agents to the brain. In this study, we investigated the feasibility of axonal trans-synaptic transport of MRI-sensitive magnetic MnFe₂O₄ (MFO) NPs from the nasal cavity to intracranially xenotransplanted glioblastoma in SCID mice. Using T1-weighted MRI, we mapped the distribution of MFO NPs and found that they accumulated in the tumor only when the glioblastoma was in direct contact with olfactory-system structures involved in nose-to-brain transport. Additionally, inhibition of axonal transport nearly abrogated the NP delivery to the tumor. Notably, olfactory-system stimulations via odor presentation significantly enhanced the nose-to-glioblastoma transport of MFO NPs. Thus, although neuronal interactions with cancer cells have detrimental effects, these interactions may also expand opportunities for targeted drug delivery during glioblastoma treatment.