title: Folate conjugated phosphorylcholine-based polycations for specific targeting in nucleic acids delivery.
abstract: Folic acid has been investigated as a targeting ligand for imaging and therapeutic agent for over a decade; however, studies on its use in targeting of nonviral gene or nucleic acids delivery systems are sparse. This study assesses potential application of a new folic acid conjugate with aminomethacrylate-phosphoryl-choline based copolymer (DMAEMA-MPC-FA) as a targeting gene delivery vector. The folate-conjugated polymers produce colloidally stable polyplexes with a particle size <200 nm and demonstrate the ability to protect DNA from enzymatic degradation to a certain extent. In cells that overexpress folate receptors (MCF-7 and KB cultures), the conjugated systems show a folate-specific association and achieved significantly enhanced transfection efficiency, compared to the nonconjugated control, with a dramatically reduced nonspecific cellular association. The transfection enhancement is achieved without a corresponding increase in cellular association, suggesting that an internal cellular trafficking of folate-conjugated system may be altered, resulting in an increased transfection efficacy. In summary, a new folate-conjugated aminomethacrylate-phosphorylcholine copolymer is capable of forming colloidal complexes with DNA, modulating their specific cell uptake and improving the level of cell transfection in folate expressing cells.
authors.affiliation: School of Pharmacy, University of Nottingham, Nottingham, UK.
authors.forename: J K W
authors.initials: JK
authors.lastname: Lam
authors.forename: S P
authors.initials: SP
authors.lastname: Armes
authors.forename: A L
authors.initials: AL
authors.lastname: Lewis
authors.forename: S
authors.initials: S
authors.lastname: Stolnik
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002412:Cations; D045744:Cell Line, Tumor; D003102:Colloids; D004247:DNA / Q000008:administration & dosage*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007624:KB Cells; D008024:Ligands; D008689:Methacrylates / Q000737:chemistry; D010316:Particle Size; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D002352:Carrier Proteins; D002412:Cations; D003102:Colloids; D058973:Folate Receptors, GPI-Anchored; D008024:Ligands; D008689:Methacrylates; D011108:Polymers; D011956:Receptors, Cell Surface; D010767:Phosphorylcholine; C070638:2-methacryloyloxyethyl phosphorylcholine; D004247:DNA; D005492:Folic Acid; C049840:2-(dimethylamino)ethyl methacrylate