Exosome-Coated Prussian Blue Nanoparticles for Specific Targeting and Treatment of Glioblastoma

Glioblastoma is one of the most aggressive and invasive types of brain cancer with a 5-year survival rate of 6.8%. With limited options, patients often have poor quality of life and are moved to palliative care after diagnosis. As a result, there is an extreme need for a novel theranostic method that allows for early diagnosis and noninvasive treatment as current peptide-based delivery standards may have off-target effects. Prussian Blue nanoparticles (PBNPs) have recently been investigated as photoacoustic imaging (PAI) and photothermal ablation agents. However, due to their inability to cross the blood-brain barrier (BBB), their use in glioblastoma treatment is limited. By utilizing a hybrid, biomimetic nanoparticle composed of a PBNP interior and a U-87 cancer cell-derived exosome coating (Exo:PB), we show tumor-specific targeting within the brain and selective thermal therapy potential due to the strong photoconversion abilities. Particle characterization was carried out and showed a complete coating around the PBNPs that contains exosome markers. In vitro cellular uptake patterns are similar to native U-87 exosomes and when exposed to an 808 nm laser, show localized cell death within the specified region. After intravenous injection of Exo:PB into subcutaneously implanted glioblastoma mice, they have shown effective targeting and eradication of tumor volume compared to PEG-coated PBNPs (PEG:PB). Through systemic administration of Exo:PB particles into orthotopic glioblastoma-bearing mice, the PBNP signal was detected in the brain tumor region through PAI. It was seen that Exo:PB had preferential tumor accumulation with less off-targeting compared to the RGD:PB control. Ex vivo analysis validated specific targeting with a direct overlay of Exo:PB with the tumor by both H&E staining and Ki67 labeling. Overall, we have developed a novel biomimetic material that can naturally cross the BBB and act as a theranostic agent for systemic targeting of glioblastoma tissue and photothermal therapeutic effect.