Design of folic acid-conjugated nanoparticles for drug targeting

The new concept developed in this study is the design of poly(ethylene glycol) (PEG)-coated biodegradable nanoparticles coupled to folic acid to target the folate-binding protein; this molecule is the soluble form of the folate receptor that is overexpressed on the surface of many tumoral cells. For this purpose, a novel copolymer, the poly[aminopoly(ethylene glycol)cyanoacrylate-co-hexadecyl cyanoacrylate] [poly(H(2)NPEGCA-co-HDCA)] was synthesized and characterized. Then nanoparticles were prepared by nanoprecipitation of the obtained copolymer, and their size, zeta potential, and surface hydrophobicity were investigated. Nanoparticles were then conjugated to the activated folic acid via PEG terminal amino groups and purified from unreacted products. Finally, the specific interaction between the conjugate folate-nanoparticles and the folate-binding protein was evaluated by surface plasmon resonance. This analysis confirmed a specific binding of the folate-nanoparticles to the folate-binding protein. This interaction did not occur with nonconjugated nanoparticles used as control. Thus. folate-linked nanoparticles represent a potential new drug carrier for tumor cell-selective targeting. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association.