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.

Keywords::

• Folate conjugate
• phosphorylcholine
• gene transfection
• nucleic acids
• delivery

Acknowledgments

The authors would like to thank Biocompatibles (UK) and The University of Nottingham (UK) for funding.

Declaration of interest: The authors report no conflicts of interest.