Folic acid-conjugated nanoparticles (NPs) of biodegradable polymer poly(lactic-co-glycolic acid) (PLGA), which were emulsified by long-chain D-a-tocopheryl polyethylene glycol succinate (vitamin E TPGS or simply TPGS) for targeted delivery of anticancer drugs, are prepared. The NPs were characterized for their size and size distribution, surface morphology, surface charge, drug encapsulation efficiency, and surface chemistry. The cellular uptake and the cytotoxicity of the drug-loaded PLGA NPs were assessed in vitro with MCF7 breast cancer cells in close comparison with the corresponding Short-chain TPGS (TPGS2k)-coated PLGA NPs and the original drug. The long-chain TPGS 2000 (TPGS2k)-emulsified PLGA NPs showed great advantages over the short-chain TPGS 1000 (TPGS1k)-emulsified and the nude PLGA NPs. The folic acid-conjugated TPGS2k-emulsified PLGA NPs showed significant advantages in cellular uptake and therapeutic effects in vitro. The IC50 value showed 90.4% less than that of the original drug. (c) 2012 American Institute of Chemical Engineers AIChE J, 2012