Paclitaxel nanopartides (PAX NPs) prepared with the size of 110 +/- 10 nm and zeta potential of -40 +/- 3 mV were encapsulated. in synthetic/biomacromolecule shell chitosan, dextran-sulfate using a layer-by-layer self-assembly technique. Zeta potential measurements, analysis of X-ray photoelectron spectroscopy, and scanning electron microscopy confirmed the successful adsorption of each layer. Surface modifications of these core-shell NPs were performed by covalently conjugating with M poly(ethylene,glycol) (H2N-PEG-carboxymethyl, M-w 3400) and fluor, escence labeled wheat germ agglutinin (F-WGA) to build a biocompa, tible and targeted drug delivery system. 32% of PAX was released from four bilayers of biomacromolecule assembled NPs within 8 h as compared With >85% of the drug released from the bare NPs. Moreover, high cell viability with PEG conjugation and high binding capacity of WGA-modified NPs with Caco-2 cells were observed This biocomptible and targeted NP-based drug delivery system, therefore, may be considered as a potential candidate for the treatment of colonic cancer and other diseases.