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 aminomethacrylatephosphoryl-choline based copolymer (DMAEMA-MPCFA) as a targeting gene delivery vector. The folate-conjugated polymers produce colloidally stable polyplexes with a particle size <200nm 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 aminomethacrylatephosphorylcholine 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. © 2009 Informa UK Ltd.