Recently, there has been an explosion of new nanomaterials with the potential to impact both medical science and human health. Translation of these discoveries to early diagnosis and effective treatment of malignancy are key clinical goals set forth by the NCI. Accordingly, this BRP is focused on the engineering of multifunctional nanoparticles that will exploit biological processes to guide the targeting, self-assembly, and remote actuation of nanoparticles to treat tumors in mouse models of cancer. The multidisciplinary team includes members with complementary expertise in biomedical engineering (Dr. Sangeeta Bhatia, MIT), chemistry and materials science (Dr. Michael Sailor, UCSD), and tumor biology (Dr. Erkki Ruoslahti, Burnham Institute) with a track record of collaborative invention, student supervision, funding, and publication. Motivated by the inefficiency of current targeting technologies, we sought to design nanoparticles that mimic the targeted accumulation of platelets at specific sites of vascular injury. We further sought to exploit the emergent properties of ensembles of nanomaterials to improve capabilities in imaging and drug delivery upon accumulation at tumor sites. Accordingly, the multifunctional nanoparticles will be based on dextran-coated iron oxide nanoparticles engineered to: (1) target tumors via phage-display derived peptides, (2) self-assemble in tumors via protease activation and plasma protein-aided trapping, (3) be detected using shifts in T2 relaxivity by MRI, and (4) deliver drugs via remote actuation using electromagnetic fields. The effort will be divided into three areas representing the expertise of the participating laboratories. The drug-loaded superparamagnetic materials will be developed and characterized by Dr. Sailor's group. Dr. Ruoslahti provides animal models of cancer, targeting expertise, and methods for identification of novel peptides via phage display. Dr. Bhatia's expertise lies in micro- and nanotechnology tools to probe cellular interfaces. Her role will be to engineer nanoparticles that can undergo triggered self-assembly, remote actuation, and in vivo imaging. The combination of these technologies and investigators is expected to lead to the development of a new generation of nanodevices that will significantly advance both medical science and treatment of cancer.