Liver cancer is among the most common and malignant human cancers in the world. The incidence of liver cancer is increasing in the United States. The majority of liver cancers are developed over long period of time, often with chronic liver disease. This offers a window of opportunity to eradicate or at least slow the progression of liver cancer. The urgent issue is to identify molecular targets that can be used for early diagnosis and therapeutic intervention. Newly available aptamer and nanoparticle technology provides a unique opportunity for this purpose. In comparison with genomic and proteomic approaches, the aptamer technology can identify markers using intact tumor cells, which will have significant advantages by closely reflecting the physiological state of cancer. The overall objective of our research program is to apply this technology to select and characterize cancer-specific aptamers for human liver cancer early diagnosis and therapy. Our previous work has validated several cancer-specific aptamers, including murine liver cancer. We have established a reliable system to isolate and culture human primary hepatocytes and liver cancer cells. We have also validated an animal model for human liver cancer. In this proposal, we will generate and test human liver cancer-specific aptamers, and validate their application in cancer diagnosis and target therapy. The goal will be achieved through three specific aims:
Aim 1 : To identify and characterize human liver cancer cell-specific aptamers;
Aim 2. To apply aptamers and nanoparticles for human liver cancer diagnosis;
Aim 3. To develop novel and effective target cancer therapy using aptamers-nanoparticle-chemotherapy agent complexes. Our investigation will identify aptamers and biomarkers for liver caner in the context of intact cancer cells. The combination of aptamer and nanoparticles will provide a powerful tool for cancer early diagnosis and targeting therapy. The experience we gain will not only be instrumental for subsequent clinical trails but also have significant impact on biomarker discovery of other solid tumors.

Public Health Relevance

Our proposal will address two of the most important issues in liver cancer management using novel aptamer/nanotechnology: discovery of effective molecular markers for early liver cancer diagnosis and validation of molecular markers for liver cancer therapy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Drug Discovery and Molecular Pharmacology Study Section (DMP)
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Forry, Suzanne L
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University of Florida
Schools of Medicine
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Zhang, Liqin; Wan, Shuo; Jiang, Ying et al. (2017) Molecular Elucidation of Disease Biomarkers at the Interface of Chemistry and Biology. J Am Chem Soc 139:2532-2540
Wan, Shuo; Zhang, Liqin; Wang, Sai et al. (2017) Molecular Recognition-Based DNA Nanoassemblies on the Surfaces of Nanosized Exosomes. J Am Chem Soc 139:5289-5292
He, Lei; Lu, Dan-Qing; Liang, Hao et al. (2017) Fluorescence Resonance Energy Transfer-Based DNA Tetrahedron Nanotweezer for Highly Reliable Detection of Tumor-Related mRNA in Living Cells. ACS Nano 11:4060-4066
You, Mingxu; Lyu, Yifan; Han, Da et al. (2017) DNA probes for monitoring dynamic and transient molecular encounters on live cell membranes. Nat Nanotechnol 12:453-459
Chen, Ke; Liu, Bo; Yu, Bo et al. (2017) Advances in the development of aptamer drug conjugates for targeted drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol 9:
Lyu, Yifan; Chen, Guang; Shangguan, Dihua et al. (2016) Generating Cell Targeting Aptamers for Nanotheranostics Using Cell-SELEX. Theranostics 6:1440-52
Wang, Ruowen; Lu, Danqing; Bai, Huarong et al. (2016) Using modified aptamers for site specific protein-aptamer conjugations. Chem Sci 7:2157-2161
Cai, Ren; Yang, Dan; Chen, Xigao et al. (2016) Three Dimensional Multipod Superstructure based on Cu(OH)2 as a Highly Efficient Nanozyme. J Mater Chem B 4:4657-4661
Lv, Yifan; Peng, Ruizi; Zhou, Yu et al. (2016) Catalytic self-assembly of a DNA dendritic complex for efficient gene silencing. Chem Commun (Camb) 52:1413-5
Liang, Hao; Xie, Sitao; Cui, Liang et al. (2016) Designing a Biostable L-DNAzyme for Lead(II) Ion Detection in Practical Samples. Anal Methods 8:7260-7264

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