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In this formulation, Doxorubicin (Dox) was conjugated to Poly (lactic-co-glycolic acid) (PLGA), and formulated via the solvent-diffusion techniques into nanoparticles. The surface of the nanoparticles was subsequently linked with Poly (ethylene glycol) (PEG) and Arg-Gly-Asp (RGD) peptide to achieve both passive and active targeting moieties. The nanoparticles were then tested against several malignant tumor cell lines. The conjugation increased loading efficiency of Dox to PLGA nanoparticles (the encapsulation efficiency was over 85%) and alleviated the drug burst release effect substantially. The drug was released from the polymeric matrix in a sustained release manner over a period of 12 days. The resultant nanoparticles were spherically uniform and well-dispersed. The nanoparticle targeting ability was proven through strong affinity to various integrin-expressing cancer cells, and much less affinity to the low integrin expression cancer cells. The nanoparticles also showed high efficacy in inducing apoptosis in specific malignant cancer cells. Taken together, these multifunctional nanoparticles hold potential to treat malignant integrin-expressing cancers. [ABSTRACT FROM PUBLISHER]