We report multifunctional nanoparticles that are capable of cancer targeting and simultaneous cancer imaging and therapy. The nanoparticles are composed of cyclic arginine-glycine-aspartic acid (cRGD) peptide ligand bioconjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) that enable loading of the anticancer drug doxorubicin (Dox). The cyclic RGD-conjugated TCL-SPION (cRGD_TCL-SPION) had a mean hydrodynamic size of 34 +/- 8 nm with approximately 0.39 wt% of cyclic RGD attached to the surface of the nanoparticles. The cRGD_TCL-SPION exhibited preferential binding towards target cancer cells (U87MG, integrin alpha(v)beta(3)+) when analyzed by T(2)- weighted magnetic resonance (MR) imaging. When Dox was loaded onto the polymeric coating layers of cRGD_TCL-SPION via ionic interaction, the resulting Dox-loaded cRGD TCL-SPION (Dox@cRGD_TCL-SPION) showed much higher cytotoxicity in U87MG cells than Dox@TCL-SPION lacking cRGD (IC(50) value of 0.02 mu M versus 0.12 mu M). These results suggest that Dox@cRGD_TCL-SPION has potential for use as an integrin-targeted, combined imaging and therapeutic agent.