"The widespread use of magnetic resonance imaging (MRI) technology in clinical and scientific research has attracted great interest in designing high relaxivity contrast agents to improve their sensitivity for the early stage detection of cancer. A number of nanostructure-based T1 contrast agents have been reported in recent years but they are still suffering some limitations for an efficient translation to in vivo applications.In this proposal, we’ll develop a novel Gd3+-loaded ultrasmall hollow mesoporous silica nanosphere (Gd-UHMSNs) platform as high sensitivity MRI probes for targeting T1-MRI of small animal tumor xenografts and potentially, of cancer patient. The specific aims for the proposal are (1) synthesize UHMSNs, and design routes to couple the particles with Gd-complexes, PEG, RGD or other targeting vectors ; (2) evaluate the relaxivity, toxicity, specific targeting capabilities of Gd-UHMSNs-RGD through tests in cell culture; and (3) evaluate the targeting agents for MRI detection of tumors in different types of mice models. Compared to the current contrast agents, the Gd-UHMSNs-RGD hopefully will show many advantages such as (1) the nanoporous and hollow structural will offer effective geometrical confinement of the Gd-complex and water molecular for enhances the r1 relaxivity, (2) the small particle size < 50 nm, high dispersivity and low toxicity is expected to avoid the RES uptake and efficiently prolong the half-time of circulation in body, (3) the RGD vectors will allow the accumulation of the particles at the tumor endothelium and at the tumor cells.Success of this project can not only provide theoretical insight to the development of nanoparticle-based high relaxivity and targeting contrast agents, but also guide us to develop a novel contrast agent for pre-scanning patients and personalized nanomedicine, resulting in great commercialization potentials."