Core-Shell Structured Chitosan-Polyethylenimine Nanoparticles for Gene Delivery: Improved Stability, Cellular Uptake, and Transfection Efficiency.

Autor: Casper J; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, CH-4056, Switzerland., Nicolle L; Group for Functionalized Biomaterials, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, CH-1015, Switzerland., Willimann M; Division of Metabolism and Children's Research Center, University Children's Hospital Zürich, Zürich, CH-8032, Switzerland., Kuzucu EÜ; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, CH-4056, Switzerland., Tran A; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, CH-4056, Switzerland., Robin P; Group for Functionalized Biomaterials, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, CH-1015, Switzerland., Detampel P; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, CH-4056, Switzerland., Grisch-Chan HM; Division of Metabolism and Children's Research Center, University Children's Hospital Zürich, Zürich, CH-8032, Switzerland., Thöny B; Division of Metabolism and Children's Research Center, University Children's Hospital Zürich, Zürich, CH-8032, Switzerland., Huwyler J; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, CH-4056, Switzerland., Gerber-Lemaire S; Group for Functionalized Biomaterials, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, CH-1015, Switzerland.
Jazyk: angličtina
Zdroj: Macromolecular bioscience [Macromol Biosci] 2023 Jan; Vol. 23 (1), pp. e2200314. Date of Electronic Publication: 2022 Oct 18.
DOI: 10.1002/mabi.202200314
Abstrakt: 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.
(© 2022 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: