Abstract: Engineered biomaterials with combined therapeutic and diagnostic (theranostic) functionalities are attractive because many diseases can be effectively treated if detected early in the disease progression. To achieve diagnostic functionality, we have been developing molecularly targeted magnetic resonance imaging contrast agents (superparamagnetic iron oxide nanoparticles). A major challenge for in vivo use of imaging contrast agents is controlling nanoparticle aggregation, which is affected by various aspects of the polymer coating on the nanoparticles and by the high levels of proteins in the blood circulation, which can adsorb to the nanoparticles. In this talk, we will discuss how the polymer coating and nature of the chemical bond anchoring the polymer to the nanoparticle surface influences the magnetic resonance response of the imaging contrast agent. We will also present results from a model based on molecular theory that predicts nanoparticle aggregation behavior in high salt solutions, which is validated in experimental measurements. We will also show how one can achieve effective targeted nucleic acid delivery in animal models of pancreatic cancer by spatially segregating molecular targeting from payload functionalities in the form of Janus nanoparticles complexed with ultrasound microbubbles.