Cancer is a worldwide disease and causes millions of deaths every year. The fatality of cancer is responsible for approximating a sixth of global death. To reduce cancer mortality, early diagnosis is one of the key factors. If cancer is diagnosed at early stage, cheaper and less invasive therapeutic strategies can be applied to increase the survival rate. Early non-invasive diagnosis methods for cancer include imaging and biomarker detection. My work mainly focused on developing nanomaterials-based probes for non-invasive cancer diagnosis through cancer imaging and biomarker quantification. Chapter 2 includes two projects of developing nanoprobes for non-invasive cancer imaging. In Project 1, we developed a robust roundtrip phase transfer approach to construct magnetic nanoparticle clusters (MNPCs) using aqueous iron oxide nanoparticles (IONPs) that were prepared by a simple, scalable, and cost-effective method. The MNPCs have the potential to serve as a contrast agent to enhance magnetic resonance imaging (MRI) contrast. In Project 2, we constructed a radioactively labeled targeted phage for single-photon emission computed tomography (SPECT). Traditional SPECT for cancer imaging relies on the Enhanced Permeability and Retention (EPR) effect. However, research has shown that the EPR effect is specific to each cancer type and patient. The radioactively labeled cancer-targeting phage could overcome the limitation of EPR effect and improve the SPECT for cancer. Chapter 3 includes two projects of developing nanoprobes for RNA biomarker quantification. In Project 3, we recruited pyropheophorbide-a (pyro) and magnetic beads to quantify small RNA. Pyro has fluorescence and can produce singlet oxygen with laser treatment. In addition, the singlet oxygen production efficiency positively correlates to the laser power. We hypothesized that the quantification based on the singlet oxygen signal would reduce the limit of detection. However, magnetic beads triggered singlet oxygen signal unexpectedly, that made this method failed to quantify target RNAs using the singlet oxygen signal. In Project 4, we developed a novel nanoparticle-based molecular beacon (NPMB). In this NPMB, the upconversion nanoparticle (UCNP) was used as a fluorophore, and the gold nanoparticle (Au NP) worked as a quencher. The exciting wavelength of UCNPs is longer than its emitting wavelength so that this method has an ultra-low background. This novel NPMB can detect both small DNA and RNA as low as aM level without purification. Overall, we developed a MNPC and a radioactively labeled targeted phage with the potential of benefit MRI and SPECT for cancer imaging, respectively, as well as two small RNA quantification strategies to quantify cancer RNA biomarker.