Abstract #2626: Nanoporous silica chip technology for the early detection of cancer and the real time assessment of chemotherapeutic efficacy
Authors: Ennio Tasciotti, Xuewu Liu, Ali Bouamrani, Ye Hu, Li Li, Ciro Chiappini, Mauro Ferrari
Journal: Cancer Research (2009)

There is an intense interest in applying proteomics to foster an improved understanding of cancer pathogenesis, develop new tumor biomarkers for diagnosis, and early detection using proteomic portrait of samples. The study of early detection of diseases can lead to significant benefits in terms of efficient and timely treatment. The blood contains a multitude of unstudied biomarkers that could reflect the ongoing physiologic state of all tissues. The low-molecular weight (LMW) region of the blood proteome is a source of diagnostic markers for diseases. The approach used to identify markers of potential diagnostic importance relies on matrix-assisted laser desorption (MALDI) mass spectrometry. In case of serum analysis, this method suffers from the interference of abundant proteins (>90% of total serum proteins), which ultimately limit the sensitivity of the detection of low abundant species in serum. We developed a novel size-exclusion strategy based on nanoporous silica chips for the efficient removal of the high molecular weight proteins and for the specific isolation and enrichment of LMW species present in complex biological mixtures. Thanks to the ability to tune the physico-chemical properties of nanoporous silica surfaces we demonstrated for the first time the correlation between pore size and molecular cut-off. We applied the Nanoporous Silica Chip Technology at the analysis of complex proteomic samples such as human plasma and developed several proteomic chips to specifically target the low molecular weight species present in the human circulating peptidome. Harvested peptides were subjected to MALDI analysis and profiles consisting of more than 300 peaks in the range 800-20 000 m/z were generated. Tunable pore sizes and surface chemistries were used as integrated \#8220;processors\#8221; for the selective depletion of the High MW protein content in serum samples and for the enrichment of LMW peptides and proteins. Reproducibility, sensitivity and protein profiles were assessed in relation to the physical (pore size, distribution, density and structure) and chemical (surface charge, hydrophobicity, hydrophilicity) properties of nanoporous silica. Our results demonstrate that nanoporous silicon chips are valuable tools for the detection of low abundant, LMW peptides in complex solutions such as serum. We envision that screenings based on our nanoporous silica chip technology may serve as a complement to histopathology, molecular imaging and other state of the art diagnostic techniques. This approach may help in the selection of individualized therapeutic combinations that target the entire cancer-specific protein network, in the real-time assessment of therapeutic efficacy and toxicity, and in the rational modulation of therapy based on changes in the cancer protein network associated with prognosis and drug resistance.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2626.