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Hartl, Natascha [VerfasserIn]; Gabold, Bettina [VerfasserIn]; Uhl, Philipp [VerfasserIn]; Kromer, Adrian [VerfasserIn]; Xiao, Ximian [VerfasserIn]; Fricker, Gert [VerfasserIn]; Mier, Walter [VerfasserIn]; Liu, Runhui [VerfasserIn]; Merkel, Olivia [VerfasserIn]

ApoE-functionalization of nanoparticles for targeted brain delivery

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  • Medientyp: E-Artikel
  • Titel: ApoE-functionalization of nanoparticles for targeted brain delivery : a feasible method for polyplexes?
  • Beteiligte: Hartl, Natascha [VerfasserIn]; Gabold, Bettina [VerfasserIn]; Uhl, Philipp [VerfasserIn]; Kromer, Adrian [VerfasserIn]; Xiao, Ximian [VerfasserIn]; Fricker, Gert [VerfasserIn]; Mier, Walter [VerfasserIn]; Liu, Runhui [VerfasserIn]; Merkel, Olivia [VerfasserIn]
  • Erschienen: 12 December 2023
  • Erschienen in: Drug Delivery and Translational Research ; 14(2024), 6, Seite 1660-1677
  • Sprache: Englisch
  • DOI: 10.1007/s13346-023-01482-w
  • ISSN: 2190-3948
  • Identifikator:
  • Schlagwörter: Apolipoprotein E ; Brain targeting ; Nylon-3 polymers ; Polyethylenimine ; Polyplexes ; siRNA delivery
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: 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.
  • Zugangsstatus: Freier Zugang