Between proteins and nanoparticles in various biofluids and their biophysical properties with respect to drug delivery and therapeutics. To this end, research groups have intently focused on determining the composition of the nanoparticle corona with human plasma, demonstrating that nanoparticle surface size and properties play a critical role in protein adsorption. Subsequent work also suggests that the protein corona is important for how the cell perceives and transports the nanoparticles. In parallel to gaining knowledge in the selective affinity of nanoparticles for proteins, research has also focused on coating the surface of nanoparticles to detect specific antigens and protein sequences. The study presented here uses nanoparticles as useful tools for enrichment and detection of low abundance proteins as a unique approach to discover new therapeutic targets. Using bioinformatics, we were able to further distinguish proteins that are uniquely adsorbed; these were validated via Western blot analysis. One of the proteins we chose to examine more closely is HDGF, which was identified as a possible ovarian-cancer-specific mitogen because it was found only with the lysates of the malignant cells, and only on the AuNPs. To date, it has not been established if HDGF has a role in ovarian cancer. However, it has been implicated in other cancers, such as melanoma, pancreatic, and lung. From our studies, we showed that in comparison to OSE, HDGF is greatly over expressed in OV 167 and A2780 cell lines. Upon knockdown of HDGF expression, we observed that the proliferation of ovarian cancer cells was vastly reduced. These results correlate strongly with previous studies which showed that HDGF is co-expressed with proliferating cell nuclear antigen in smooth muscle cells. These results demonstrate, for the first time, a possible role of HDGF in ovarian cancer pathogenesis and present it as a potential therapeutic target. They also introduce a new methodology of exploiting nanoparticle corona content to identify potential therapeutics. In summary, this paper employs a unique combination of tools: proteomics, bioinformatics, and nanotechnology, to open up a new avenue for identifying and validating new therapeutic targets in cancer. Using surface-modified gold nanoparticles, we successfully enriched low-abundance proteins from lysates of normal and malignant ovarian cancer cells and identified them using a combination of proteomics and bioinformatics analysis. Although we focused on HDGF in this study, extension of similar methods to other protein targets to target other diseases would be valid. Future studies will focus on the evolution, modulation, and identification of protein coronas over time and also on testing this unique system with human patient samples.