Nose-to-Brain\nDelivery of Biomimetic Nanoparticles\nfor Glioblastoma Targeted Therapy

Glioblastoma (GBM)\nis an extremely aggressive form of brain cancer\nthat remains challenging to treat, especially owing to the lack of\neffective targeting and drug delivery concerns. Due to its anatomical\nadvantages, the nose-to-brain strategy is an interesting route for\ndrug delivery. Nanoengineering has provided technological tools and\ninnovative strategies to overcome biotechnological limitations, which\nis promising for improving the effectiveness of conventional therapies.\nHerein, we designed a biomimetic multifunctional nanostructure produced\nby polymeric poly(d,l-lactic-<i>co</i>-glycolic)\nacid (PLGA) core loaded with Temozolomide (TMZ) coated with cell membrane\nisolated from glioma cancer cells. The developed nanostructures (NP-MB)\nwere fully characterized, and their biological performance was investigated\nextensively. The results indicate that NP-MB could control TMZ release\nand promote TMZ permeation in the <i>ex vivo</i> nasal porcine\nmucosa. The higher cytotoxicity of NP-MB in different glioma cell\nlines, particularly against U251 cells, reinforces their potential\nfor homotypic targeting. The chicken chorioallantoic membrane assay\nrevealed a tumor size reduction and antiangiogenic activity. <i>In vivo</i> biodistribution studies showed that NP-MB effectively\nreaches the brain following nasal administration. These findings suggest\nthat NP-MB holds promise as a biomimetic nanoplatform for effective\ntargeting and homotypic recognition in GBM therapy with high potential\nfor clinical translation.