RRC ID 74813
Author Casper J, Nicolle L, Willimann M, Kuzucu EÜ, Tran A, Robin P, Detampel P, Grisch-Chan HM, Thöny B, Huwyler J, Gerber-Lemaire S.
Title Core-Shell Structured Chitosan-Polyethylenimine Nanoparticles for Gene Delivery: Improved Stability, Cellular Uptake, and Transfection Efficiency.
Journal Macromol Biosci
Abstract The delivery of nucleic acids relies on vectors that condense and encapsulate their cargo. Especially nonviral gene delivery systems are of increasing interest. However, low transgene expression levels and limited tolerability of these systems remain a challenge. The improvement of nucleic acid delivery using depolymerized chitosan-polyethylenimine DNA complexes (dCS-PEI/DNA) is investigated. The secore complexes are further combined with chitosan-based shells and functionalized with polyethylene glycol (PEG) and cell penetrating peptides. This modular approach allows to evaluate the effect of functional shell components on physicochemical particle characteristics and biological effects. The optimized ternary complex combines a core-dCS-linear PEI/DNA complex with a shell consisting of dCS-PEG-COOH, which results in improved nucleic acid encapsulation, cellular uptake and transfection potency in human hepatoma HuH-7cells and murine primary hepatocytes. Effects on transgene expression are confirmed in wild-type mice following retrograde intrabiliary infusion. After administration of only 100 ng complexed DNA, ternary complexes induced a high reporter gene signal for three days. It is concluded that ternary coreshell structured nanoparticles comprising functionalized chitosan can be used for in vitro andin vivo gene delivery.
Volume 23(1)
Pages e2200314
Published 2023-1-1
DOI 10.1002/mabi.202200314
PMID 36200651
MeSH Animals Chitosan* / chemistry Chitosan* / pharmacology DNA / genetics Gene Transfer Techniques Humans Mice Nanoparticles* / chemistry Polyethylene Glycols / chemistry Polyethylene Glycols / pharmacology Polyethyleneimine / chemistry Polyethyleneimine / pharmacology Transfection
IF 3.416
Human and Animal Cells HuH-7