Here, we report a nanotheranostic system that enables simultaneous imaging and therapy of HER2-overexpressing tumors. We first screened an aptide-based phage library for HER2-specific peptide ligands, identifying a HER2-specific aptide (APT(HER2)) phage clone. Chemically synthesized APT(HER2) showed high affinity for its target protein (K-d approximate to 89 nM) and specifically bound HER2-overexpressing cells (NIH3T6.7) and tumor tissue slices. Next, we prepared HER2-specific-aptide-conjugated magnetonanoclusters (APT(HER2)-MNCs) by a rehydration method using oleic acid-stabilized superparamagnetic iron oxide nanoparticles (SPIONs) and amphiphilic phospholipids, yielding nanoparticles with a hydrodynamic diameter of 47 +/- 10 nm. The APT(HER2)-MNCs showed higher transverse (r(2)) relaxivity (similar to 180 mM(-1) s(-1)) and greater drug-loading capacity compared to the equivalent isolated SPIONs (similar to 120 mM(-1) s(-1)). When intravenously injected into HER2-overexpressing NIH3T6.7 tumor-bearing mice, APT(HER2)-MNCs substantially accumulated in tumor tissue, enhancing the relative signal by similar to 45% at 3 h post-injection. This allowed us to detect the tumor using magnetic resonance imaging. Furthermore, after docetaxel loading, the drug-loaded APT(HER2)-MNCs remarkably inhibited the growth of HER2-overexpressing tumors (similar to 50% relative to controls) with little apparent toxicity, measured as changes in body weight. Together, these results indicate that APT(HER2)-MNCs show promise as an efficient nanotheranostic system that enables specific cancer imaging as well as targeted therapy.