Abstract An on-going effort in the field of nanomedicine is to develop nanoplatforms with both imaging and therapeutic functions, the so-called “nano-theranostics”. We have previously developed a human serum albumin (HSA) coated iron oxide nanoparticle (HINP) formula and used multiple imaging modalities to validate its tumor targeting attributes. In the current study, we sought to impart doxorubicin (Dox) onto the HINPs and to assess the potential of the conjugates as theranostic agents. In a typical preparation, we found that about 0.5 mg of Dox and 1 mg of iron oxide nanoparticles (IONPs, Fe content) could be loaded into 10 mg of HSA matrices. The resulting Dox-loaded HINPs (D-HINPs) retained a tumor targeting capability, as manifested by both in vivo MRI and ex vivo immunostaining studies. For therapeutic studies, 25 4T1 tumor mice were divided into 5 groups (5 mice/group), and were treated with 1) D-HINPs (3 mg Dox/kg); 2) free Dox (3 mg Dox/kg); 3) Doxil (3 mg Dox/kg); 4) HINPs and 5) PBS. For Group 4, HINPs were injected at the same Fe concentration as in Group 1. The drugs (including controls) were given every other day for a total of 4 doses. A dramatic increase in tumor volume was found in the PBS control group. The group injected with HINPs manifested a tumor growth pattern that was similar to the PBS group and showed no weight loss throughout the treatment, indicating that the HINPs alone had neither therapeutic nor toxic effects in the studied mice. Compared with the control group, the injection of Dox led to some tumor suppression in the first week of treatment but gradually lost efficacy. D-HINPs showed a striking tumor suppression effect that was comparable to Doxil and that greatly outperformed free Dox. Such a strategy can be readily extended to load other types of small molecules, making HINP a promising theranostic nanoplatform. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4437. doi:10.1158/1538-7445.AM2011-4437