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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA133086-04
Application #
8267110
Study Section
Drug Discovery and Molecular Pharmacology Study Section (DMP)
Program Officer
Forry, Suzanne L
Project Start
2009-07-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$294,868
Indirect Cost
$93,593
Name
University of Florida
Department
Pathology
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Lyu, Yifan; Chen, Guang; Shangguan, Dihua et al. (2016) Generating Cell Targeting Aptamers for Nanotheranostics Using Cell-SELEX. Theranostics 6:1440-52
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
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 Mater Biol Med 4:4657-4661
Long, Yuqian; Qin, Zhiqiang; Duan, Minlan et al. (2016) Screening and identification of DNA aptamers toward Schistosoma japonicum eggs via SELEX. Sci Rep 6:24986
Cui, Liang; Peng, Ruizi; Fu, Ting et al. (2016) Biostable L-DNAzyme for Sensing of Metal Ions in Biological Systems. Anal Chem 88:1850-5
Ocsoy, Ismail; Isiklan, Nuran; Cansiz, Sena et al. (2016) ICG-conjugated Magnetic Graphene Oxide for Dual Photothermal and Photodynamic Therapy. RSC Adv 6:30285-30292
Li, Juan; Mo, Liuting; Lu, Chun-Hua et al. (2016) Functional nucleic acid-based hydrogels for bioanalytical and biomedical applications. Chem Soc Rev 45:1410-31
Jin, Cheng; Qiu, Liping; Li, Jin et al. (2016) Cancer biomarker discovery using DNA aptamers. Analyst 141:461-6
Duan, Minlan; Long, Yuqian; Yang, Cai et al. (2016) Selection and characterization of DNA aptamer for metastatic prostate cancer recognition and tissue imaging. Oncotarget 7:36436-36446
Lv, Yifan; Cui, Liang; Peng, Ruizi et al. (2015) Entropy Beacon: A Hairpin-Free DNA Amplification Strategy for Efficient Detection of Nucleic Acids. Anal Chem 87:11714-20

Showing the most recent 10 out of 120 publications