ApoE-functionalization of nanoparticles for targeted brain delivery

• Verfasst von: Hartl, Natascha [VerfasserIn]
• Verfasst von: Gabold, Bettina [VerfasserIn]
• Verfasst von: Uhl, Philipp [VerfasserIn]
• Verfasst von: Kromer, Adrian [VerfasserIn]
• Verfasst von: Xiao, Ximian [VerfasserIn]
• Verfasst von: Fricker, Gert [VerfasserIn]
• Verfasst von: Mier, Walter [VerfasserIn]
• Verfasst von: Liu, Runhui [VerfasserIn]
• Verfasst von: Merkel, Olivia [VerfasserIn]
• Titel: ApoE-functionalization of nanoparticles for targeted brain delivery
• Titelzusatz: a feasible method for polyplexes?
• Verf.angabe: Natascha Hartl, Bettina Gabold, Philipp Uhl, Adrian Kromer, Ximian Xiao, Gert Fricker, Walter Mier, Runhui Liu, Olivia M. Merkel
• E-Jahr: 2023
• Jahr: 12 December 2023
• Umfang: 18 S.
• Fussnoten: Gesehen am 08.05.2024
• Titel Quelle: Enthalten in: Drug Delivery and Translational Research
• Ort Quelle: New York, NY [u.a.] : Springer, 2011
• Jahr Quelle: 2024
• Band/Heft Quelle: 14(2024), 6, Seite 1660-1677
• ISSN Quelle: 2190-3948
• DOI: doi:10.1007/s13346-023-01482-w
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Apolipoprotein E
• Sach-SW: Brain targeting
• Sach-SW: Nylon-3 polymers
• Sach-SW: Polyethylenimine
• Sach-SW: Polyplexes
• Sach-SW: siRNA delivery
• K10plus-PPN: 1888137657

Abstract

The blood-brain barrier (BBB) poses a major obstacle in the treatment of all types of central nervous system (CNS) diseases. Small interfering RNA (siRNA) offers in principle a promising therapeutic approach by downregulating disease-related genes via RNA interference. However, the BBB is a formidable barrier for macromolecules such as nucleic acids. In an effort to develop a brain-targeted strategy for siRNA delivery systems formed by electrostatic interactions with cationic polymers (polyplexes (PXs)), we investigated the suitability of the well-known surfactant-based approach for Apolipoprotein E (ApoE)-functionalization of nanoparticles (NPs). The aim of this present work was to investigate if ApoE coating of siRNA PXs formed with cationic branched 25-kDa poly(ethyleneimine) (b-PEI) and nylon-3 polymers without or after precoating with polysorbate 80 (PS 80) would promote successful delivery across the BBB. We utilized highly hydrophobic NM0.2/CP0.8 nylon-3 polymers to evaluate the effects of hydrophobic cyclopentyl (CP) subunits on ApoE binding efficacy and observed successful ApoE binding with and without PS 80 precoating to the nylon-3 but not the PEI polyplexes. Accordingly, ApoE-coated nylon-3 polyplexes showed significantly increased uptake and gene silencing in U87 glioma cells but no benefit in vivo. In conclusion, further optimization of ApoE-functionalized polyplexes and more sophisticated in vitro models are required to achieve more successful in vitro-in vivo translation in future approaches.