title: Degradable cationic nanohydrogel particles for stimuli-responsive release of siRNA.
abstract: Well-defined nanogels have become quite attractive as safe and stable carriers for siRNA delivery. However, to avoid nanoparticle accumulation, they need to provide a stimuli-responsive degradation mechanism that can be activated at the payload's site of action. In this work, the synthetic concept for generating well-defined nanohydrogel particles is extended to incorporate disulfide cross-linkers into a cationic nanonetwork for redox-triggered release of oligonucleotide payload as well as nanoparticle degradation under reductive conditions of the cytoplasm. Therefore, a novel disulfide-modified spermine cross-linker is designed that both allows disassembly of the nanogel as well as removal of cationic charge from residual polymer fragments. The degradation process is monitored by scanning electron microscopy (SEM) and fluorescence correlation spectroscopy (FCS). Moreover, siRNA release is analyzed by agarose gel electrophoresis and a fluorescent RNA detection assay. The results exemplify the versatility of the applied nanogel manufacturing process, which allows alternative stimuli-responsive core cross-linkers to be integrated for triggered oligonucleotide release as well as effective biodegradation for reduced nanotoxicity.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, D-55099, Mainz, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Nuhn
authors.forename: Lydia
authors.initials: L
authors.lastname: Braun
authors.forename: Iris
authors.initials: I
authors.lastname: Overhoff
authors.forename: Annette
authors.initials: A
authors.lastname: Kelsch
authors.forename: David
authors.initials: D
authors.lastname: Schaeffel
authors.forename: Kaloian
authors.initials: K
authors.lastname: Koynov
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zentel
mesh_terms: D002412:Cations; D004220:Disulfides / Q000138:chemical synthesis; D020100:Hydrogels / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism*; D013095:Spermidine / Q000737:chemistry
chemical_list: D002412:Cations; D004220:Disulfides; D020100:Hydrogels; D000080385:Nanogels; D034741:RNA, Small Interfering; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D013095:Spermidine
keywords: cationic nanohydrogels; degradable nanogels; redox-responsive carriers; siRNA delivery; stimuli-responsive release