title: Modular construction of multifunctional bioresponsive cell-targeted nanoparticles for gene delivery.
abstract: Multifunctional and modular block copolymers prepared from biocompatible monomers and linked by a bioreducible disulfide linkage have been prepared using a combination of ring-opening and atom-transfer radical polymerizations (ATRP). The presence of terminal functionality via ATRP allowed cell-targeting folic acid groups to be attached in a controllable manner, while the block copolymer architecture enabled well-defined nanoparticles to be prepared by a water-oil-water double emulsion procedure to encapsulate DNA with high efficiency. Gene delivery assays in a Calu-3 cell line indicated specific folate-receptor-mediated uptake of the nanoparticles, and triggered release of the DNA payload via cleavage of the disulfide link resulted in enhanced transgene expression compared to nonbioreducible analogues. These materials offer a promising and generic means to deliver a wide variety of therapeutic payloads to cells in a selective and tunable way.
authors.affiliation: School of Pharmacy and School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
authors.forename: Aram O
authors.initials: AO
authors.lastname: Saeed
authors.forename: Johannes P
authors.initials: JP
authors.lastname: Magnusson
authors.forename: Emilia
authors.initials: E
authors.lastname: Moradi
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Soliman
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wang
authors.forename: Snow
authors.initials: S
authors.lastname: Stolnik
authors.forename: Kristofer J
authors.initials: KJ
authors.lastname: Thurecht
authors.forename: Steven M
authors.initials: SM
authors.lastname: Howdle
authors.forename: Cameron
authors.initials: C
authors.lastname: Alexander
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000378:metabolism; D008954:Models, Biological; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D011108:Polymers; D004247:DNA; D005492:Folic Acid; D008156:Luciferases