Design of folic acid-conjugated nanoparticles for drug targeting

The new concept developed in this study is the design of poly(ethylene glyc ol) (PEG)-coated biodegradable nanoparticles coupled to folic acid to targe t the folate-binding protein; this molecule is the soluble form of the fola te receptor that is overexpressed on the surface of many tumoral cells. For this purpose, a novel copolymer, the poly[aminopoly(ethylene glycol)cyanoa crylate-co-hexadecyl cyanoacrylate] [poly(H(2)NPEGCA-co-HDCA)] was synthesi zed and characterized. Then nanoparticles were prepared by nanoprecipitatio n of the obtained copolymer, and their size, zeta potential, and surface hy drophobicity were investigated. Nanoparticles were then conjugated to the a ctivated folic acid via PEG terminal amino groups and purified from unreact ed products. Finally, the specific interaction between the conjugate folate -nanoparticles and the folate-binding protein was evaluated by surface plas mon resonance. This analysis confirmed a specific binding of the folate-nan oparticles to the folate-binding protein. This interaction did not occur wi th nonconjugated nanoparticles used as control. Thus. folate-linked nanopar ticles represent a potential new drug carrier for tumor cell-selective targ eting. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceutical Associatio n.