title: Multicomponent synthetic polymers with viral-mimetic chemistry for nucleic acid delivery.
abstract: The ability to deliver genetic material for therapy remains an unsolved challenge in medicine. Natural gene carriers, such as viruses, have evolved sophisticated mechanisms and modular biopolymer architectures to overcome these hurdles. Here we describe synthetic multicomponent materials for gene delivery, designed with features that mimic virus modular components and which transfect specific cell lines with high efficacy. The hierarchical nature of the synthetic carriers allows the incorporation of membrane-disrupting peptides, nucleic acid binding components, a protective coat layer, and an outer targeting ligand all in a single nanoparticle, but with functionality such that each is utilized in a specific sequence during the gene delivery process. The experimentally facile assembly suggests these materials could form a generic class of carrier systems that could be customized for many different therapeutic settings.
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Soliman
authors.forename: Rujikan
authors.initials: R
authors.lastname: Nasanit
authors.forename: Samer R
authors.initials: SR
authors.lastname: Abulateefeh
authors.forename: Stephanie
authors.initials: S
authors.lastname: Allen
authors.forename: Martyn C
authors.initials: MC
authors.lastname: Davies
authors.forename: Simon S
authors.initials: SS
authors.lastname: Briggs
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Seymour
authors.forename: Jon A
authors.initials: JA
authors.lastname: Preece
authors.forename: Anna M
authors.initials: AM
authors.lastname: Grabowska
authors.forename: Susan A
authors.initials: SA
authors.lastname: Watson
authors.forename: Cameron
authors.initials: C
authors.lastname: Alexander
mesh_terms: D040761:Biomimetic Materials / Q000009:adverse effects / Q000737:chemistry*; D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism; D004705:Endocytosis; D005027:Ethylene Oxide / Q000009:adverse effects / Q000737:chemistry; D018014:Gene Transfer Techniques / Q000009:adverse effects; D045325:HCT116 Cells; D018922:HL-60 Cells; D006461:Hemolysis; D006801:Humans; D008024:Ligands; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009696:Nucleic Acids / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry; D011073:Polyamines / Q000009:adverse effects / Q000737:chemistry; D000071228:Polyelectrolytes; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry*; D011990:Receptors, Transferrin / Q000378:metabolism; D013499:Surface Properties; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D005027:Ethylene Oxide; D008024:Ligands; D009363:Neoplasm Proteins; D009696:Nucleic Acids; D010455:Peptides; D011073:Polyamines; D000071228:Polyelectrolytes; D011092:Polyethylene Glycols; D011108:Polymers; D011990:Receptors, Transferrin; D014168:Transferrin