title: Comparing Gene Silencing and Physiochemical Properties in siRNA Bound Cationic Star-Polymer Complexes.
abstract: The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition-Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle tracking analysis we have characterized the nanoscale morphology, stiffness, and surface charge of the complexes with and without the protein corona. This is one of the first examples of a comprehensive physiochemical analysis of siRNA-polymer complexes being performed alongside in vitro biological assays, allowing us to describe a set of desirable physical features of cationic polymer complexes that promote gene silencing. Multifaceted studies such as this will improve our understanding of structure-function relationships in nanotherapeutics, facilitating the rational design of polymer-mediated siRNA delivery systems for novel treatment strategies.
authors.affiliation: CSIRO-Health and Biosecurity Business Unit, Australian Animal Health Laboratory , 5 Portarlington Road, Geelong, Vic 3220, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Dearnley
authors.affiliation: ARC Training Centre for Biodevices, Swinburne University of Technology , Hawthorn, Vic 3122, Australia.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Reynolds
authors.affiliation: CSIRO-Manufacturing Business Unit, Bayview Avenue, Clayton, Vic 3168, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Cass
authors.affiliation: CSIRO-Manufacturing Business Unit, Bayview Avenue, Clayton, Vic 3168, Australia.|College of Materials Science and Engineering, Beijing University of Chemical Technology , Beijing 100029, China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Wei
authors.affiliation: CSIRO-Health and Biosecurity Business Unit, Australian Animal Health Laboratory , 5 Portarlington Road, Geelong, Vic 3220, Australia.
authors.forename: Shuning
authors.initials: S
authors.lastname: Shi
authors.affiliation: CSIRO-Health and Biosecurity Business Unit, Australian Animal Health Laboratory , 5 Portarlington Road, Geelong, Vic 3220, Australia.
authors.forename: A Aalam
authors.initials: AA
authors.lastname: Mohammed
authors.affiliation: CSIRO-Manufacturing Business Unit, Bayview Avenue, Clayton, Vic 3168, Australia.
authors.forename: Tam
authors.initials: T
authors.lastname: Le
authors.affiliation: CSIRO-Manufacturing Business Unit, Bayview Avenue, Clayton, Vic 3168, Australia.
authors.forename: Pathiraja
authors.initials: P
authors.lastname: Gunatillake
authors.affiliation: CSIRO-Health and Biosecurity Business Unit, Australian Animal Health Laboratory , 5 Portarlington Road, Geelong, Vic 3220, Australia.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Tizard
authors.affiliation: CSIRO-Manufacturing Business Unit, Bayview Avenue, Clayton, Vic 3168, Australia.
authors.forename: San H
authors.initials: SH
authors.lastname: Thang
authors.affiliation: CSIRO-Health and Biosecurity Business Unit, Australian Animal Health Laboratory , 5 Portarlington Road, Geelong, Vic 3220, Australia.
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Hinton
mesh_terms: D002412:Cations / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D020868:Gene Silencing / Q000187:drug effects*; D018014:Gene Transfer Techniques; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics
chemical_list: D002412:Cations; D011108:Polymers; D034741:RNA, Small Interfering