Nose-to-Brain Delivery of Biomimetic Nanoparticles for Glioblastoma Targeted Therapy

Author(s)

Ferreira, Natalia Noronha ; Leite, Celisnolia Morais ; Moreno, Natalia Sanchez ; Miranda, Renata Rank ; Lins, Paula Maria Pincela ; Rodero, Camila Fernanda ; de Oliveira Junior, Edilson ; Lima, Eliana Martins ; Reis, Rui M. ; Zucolotto, Valtencir

• Document type: Journal article
• Source: ACS APPLIED MATERIALS & INTERFACES; v. 17, n. 1, p. 16-pg., 2024-12-18.

Abstract

Glioblastoma (GBM) is an extremely aggressive form of brain cancer that remains challenging to treat, especially owing to the lack of effective targeting and drug delivery concerns. Due to its anatomical advantages, the nose-to-brain strategy is an interesting route for drug delivery. Nanoengineering has provided technological tools and innovative strategies to overcome biotechnological limitations, which is promising for improving the effectiveness of conventional therapies. Herein, we designed a biomimetic multifunctional nanostructure produced by polymeric poly(d,l-lactic-co-glycolic) acid (PLGA) core loaded with Temozolomide (TMZ) coated with cell membrane isolated from glioma cancer cells. The developed nanostructures (NP-MB) were fully characterized, and their biological performance was investigated extensively. The results indicate that NP-MB could control TMZ release and promote TMZ permeation in the ex vivo nasal porcine mucosa. The higher cytotoxicity of NP-MB in different glioma cell lines, particularly against U251 cells, reinforces their potential for homotypic targeting. The chicken chorioallantoic membrane assay revealed a tumor size reduction and antiangiogenic activity. In vivo biodistribution studies showed that NP-MB effectively reaches the brain following nasal administration. These findings suggest that NP-MB holds promise as a biomimetic nanoplatform for effective targeting and homotypic recognition in GBM therapy with high potential for clinical translation. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/25645-0 - BIOINSPIRED AND BIOMIMETIC NANOSTRUCTURED SYSTEMS FOR NOSE-TO-BRAIN ADMINISTRATION: A NOVEL PERSPECTIVE FOR GLIOBLASTOMA THERAPY
• Grantee: Natália Noronha Ferreira Naddeo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/00124-5 - Functionalization of nanomaterials for cancer therapy
• Grantee: Valtencir Zucolotto
• Support Opportunities: Regular Research Grants