The goal of this research is to develop a novel targeted protease sensing nanomedicine for early detection and treatment of ovarian cancer. Currently micrometastases within the abdominal cavity is detected by naked eyes;therefore high missing rate has caused recurrence in about 80?90% of women with ovarian cancer. A reliable imaging probe to report micrometastases would be extremely useful in disease management. It has been found that the protease activity of cathepsin B and high level of folate receptor were associated with ovarian cancer. Taking advantages of these unique expression patterns of folate receptor and cathepsin B, we propose to develop a novel nanomedicine with ultra- sensitivity for imaging and specific cytotoxicity for treatment. The assembled nanomedicines are neither fluorescent nor cytotoxic in its initial intact state, but become brightly fluorescent and phototoxic after selective internalization and intracellular activation. The newly developed nanomedicines are expected to have several advantages to treat ovarian cancer: a) high specificity because of regional specific uptake mechanism, b) high sensitivity and potency because of the unique activation mechanism, and c) improved surgical outcome because oncologists could resect micrometastases in completion. Together with recent advances in the field of optical imaging systems, this research is expected to ultimately result in a new clinical photomedicine to help ovarian cancer patients. We believe that the developed approach can be used as a platform to design a broad spectrum of activatable nanomedicine to image and treat other epithelial cancers. Narrative The overall goal of this research is to develop a novel targeted enzyme sensitive nanomedicine to image and treat ovarian cancer. The proposed technology is unique and there are currently no alternatives available for ovarian cancer imaging. The proposed nanomedicine could have vast translational potential and could be introduced into the clinic fairly rapidly following efficacy testing in animal models.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA135312-05
Application #
8267728
Study Section
Special Emphasis Panel (ZRG1-NANO-M (02))
Program Officer
Menkens, Anne E
Project Start
2008-08-07
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$301,913
Indirect Cost
$100,638
Name
Methodist Hospital Research Institute
Department
Type
DUNS #
185641052
City
Houston
State
TX
Country
United States
Zip Code
77030
Lee, Seung Koo; Mortensen, Luke J; Lin, Charles P et al. (2014) An authentic imaging probe to track cell fate from beginning to end. Nat Commun 5:5216
Lee, Jae Sam; Tung, Ching-Hsuan (2013) Osteotropic cancer diagnosis by an osteocalcin inspired molecular imaging mimetic. Biochim Biophys Acta 1830:4621-7
Abd-Elgaliel, Wael R; Cruz-Monserrate, Zobeida; Wang, Huamin et al. (2013) Pancreatic cancer-associated Cathepsin E as a drug activator. J Control Release 167:221-7
Lee, Jae Sam; Tung, Ching-Hsuan (2013) Lipo-oligoarginine-based intracellular delivery. Methods Mol Biol 991:281-92
Han, Junyan; Han, Myung Shin; Tung, Ching-Hsuan (2013) A fluorogenic probe for *-galactosidase activity imaging in living cells. Mol Biosyst 9:3001-8
Han, Junyan; Han, Myung Shin; Tung, Ching-Hsuan (2013) A non-toxic fluorogenic dye for mitochondria labeling. Biochim Biophys Acta 1830:5130-5
Han, Junyan; Engler, Anthony; Qi, Jianjun et al. (2013) Ultra Pseudo-Stokes Shift Near Infrared Dyes Based on Energy Transfer. Tetrahedron Lett 54:502-505
Abd-Elgaliel, Wael R; Tung, Ching-Hsuan (2013) Exploring the structural requirements of collagen-binding peptides. Biopolymers 100:167-73
Qi, Jianjun; Han, Myung Shin; Tung, Ching-Hsuan (2012) A benzothiazole alkyne fluorescent sensor for Cu detection in living cell. Bioorg Med Chem Lett 22:1747-9
Qi, Jianjun; Han, Myung-Shin; Chang, Yu-Cheng et al. (2011) Developing visible fluorogenic 'click-on' dyes for cellular imaging. Bioconjug Chem 22:1758-62

Showing the most recent 10 out of 20 publications