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We reported the development of multifunctional poly (lactic-co-glycolic acid) (PLGA)-lecithin-polyethylene glycol (PEG) core-shell nanoparticles (NPs) that combined the beneficial properties of liposome and polymeric NPs for chemotherapeutics delivery. The particle size, surface charge and surface functional groups were easily tunable in highly reproducible manner by various formulation parameters such as lipid/polymer, 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG-COOH/lecithin, DSPE-PEG-COOH/DSPE-PEG-NH2 mass ratio and modification of terminal groups of DSPE-PEG. We encapsulated model chemotherapy drug, hydrophilic cisplatin (DDP) or hydrophobic DDP prodrug, in the NPs and showed high encapsulation efficiency, excellent stability, specific FA targeting recognition for MCF-7 cells with over FA receptors expression and pretty cytotoxicity. Such PLGA–lecithin–PEG core-shell nanoparticles (NPs) were proved to be a promising drug delivery nanocarrier for cancer-targeted therapy.