Multifunctional Fluoropolymer‐Engineered Magnetic Nanoparticles to Facilitate Blood‐Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma

Autor: Helen Forgham, Jiayuan Zhu, Xumin Huang, Cheng Zhang, Heather Biggs, Liwei Liu, Yi Cheng Wang, Nicholas Fletcher, James Humphries, Gary Cowin, Karine Mardon, Maria Kavallaris, Kristofer Thurecht, Thomas P. Davis, Ruirui Qiao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 25, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202401340
Popis: Abstract Patients with brain cancers including medulloblastoma lack treatments that are effective long‐term and without side effects. In this study, a multifunctional fluoropolymer‐engineered iron oxide nanoparticle gene‐therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum. The blood‐brain barrier (BBB) tailored system demonstrates enhanced BBB penetration, facilitates delivery of functionally active siRNA to medulloblastoma cells, and delivers a significant, almost complete block in protein expression within an in vitro extracellular acidic environment (pH 6.7) – as favored by most cancer cells. In vivo, it effectively crosses an intact BBB, provides contrast for magnetic resonance imaging (MRI), and delivers siRNA capable of slowing tumor growth without causing signs of toxicity – meaning it possesses a safe theranostic function. The pioneering methodology applied shows significant promise in the advancement of brain and tumor microenvironment‐focused MRI‐siRNA theranostics for the better treatment and diagnosis of medulloblastoma.
Databáze: Directory of Open Access Journals
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