DEVELOPING SURFACE-MODIFIED LANTHANIDE-DOPED NANOPARTICLES AS A BRAIN TUMOR THERANOSTICS

Abstract

Glioblastoma (GBM), a grade IV astrocytoma is highly aggressive and lethal. Recently, nano-based systems were widely used in GBM studies because of the ability to traverse the blood-brain-barrier successfully. However, there are still several major challenges. Lanthanide-doped nanoparticles (Ln-doped NPs) have garnered immense potential for many biological studies but not much was utilized in GBM.

This thesis will outline the exploration of Ln-doped NPs for GBM nanotheranostic studies. In the first work, we showed direct evidence using bioimaging and electron microscopy studies for nanotheranostic trafficking into GBM in an intracranial human GBM mouse model. Besides, we developed a low-dose metronomic nanotheranostic (MetNano) regimen and showed an augmented direct anti-tumor effect from NPs in GBM that were previously overlooked in other MetNano regimen studies. In second work, we developed a dual-site targeting strategy using Ln-doped NPs against an intracranial human GBM mouse model and demonstrated enhanced delivery and improved the mice’s overall survival.