title: Approach to Rapid Synthesis and Functionalization of Iron Oxide Nanoparticles for High Gene Transfection.
abstract: Surface functionalization of theranostic nanoparticles (NPs) typically relies on lengthy, aqueous postsynthesis labeling chemistries that have limited ability to fine-tune surface properties and can lead to NP heterogeneity. The need for a rapid, simple synthesis approach that can provide great control over the display of functional moieties on NP surfaces has led to increased use of highly selective bioorthoganol chemistries including metal-affinity coordination. Here we report a simple approach for rapid production of a superparamagnetic iron oxide NPs (SPIONs) with tunable functionality and high reproducibility under aqueous conditions. We utilize the high affinity complex formed between catechol and Fe((III)) as a means to dock well-defined catechol modified polymer modules on the surface of SPIONs during sonochemical coprecipitation synthesis. Polymer modules consisted of chitosan and poly(ethylene glycol) (PEG) copolymer (CP) modified with catechol (CCP), and CCP functionalized with cationic polyethylenimine (CCP-PEI) to facilitate binding and delivery of DNA for gene therapy. This rapid synthesis/functionalization approach provided excellent control over the extent of PEI labeling, improved SPION magnetic resonance imaging (MRI) contrast enhancement and produced an efficient transfection agent.
authors.affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Stephen
authors.affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Dayringer
authors.affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Josh J
authors.initials: JJ
authors.lastname: Lim
authors.affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Revia
authors.affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Mackenzie V
authors.initials: MV
authors.lastname: Halbert
authors.affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Mike
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Biochemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Arvind
authors.initials: A
authors.lastname: Bakthavatsalam
authors.affiliation: Department of Neurological Surgery, University of Washington , Seattle, Washington 98195, United States.|Department of Radiology, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
authors.affiliation: Department of Materials Science and Engineering, University of Washington , Seattle, Washington 98195, United States.|Department of Neurological Surgery, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D002396:Catechols / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection / Q000379:methods*
chemical_list: D002396:Catechols; D020099:Coated Materials, Biocompatible; D005290:Ferric Compounds; C000499:ferric oxide; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C034221:catechol; C000595209:polyethylene glycol 1000
keywords: cancer; gene therapy; iron oxide; nanomaterials; theranostics