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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-NANO-M (02))
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Menkens, Anne E
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Methodist Hospital Research Institute
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Lee, Seung Koo; Law, Benedict; Tung, Ching-Hsuan (2017) Versatile Nanodelivery Platform to Maximize siRNA Combination Therapy. Macromol Biosci 17:
Lee, Seung Koo; Tung, Ching-Hsuan (2016) siRNA Nanoparticles for Ultra-Long Gene Silencing In Vivo. Methods Mol Biol 1372:113-20
Tung, Ching-Hsuan; Qi, Jianjun; Hu, Lingchuan et al. (2015) A Quick Responsive Fluorogenic pH Probe for Ovarian Tumor Imaging. Theranostics 5:1166-74
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
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) Osteotropic cancer diagnosis by an osteocalcin inspired molecular imaging mimetic. Biochim Biophys Acta 1830:4621-7
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 non-toxic fluorogenic dye for mitochondria labeling. Biochim Biophys Acta 1830:5130-5
Lee, Seung Koo; Tung, Ching-Hsuan (2013) A fabricated siRNA nanoparticle for ultra-long gene silencing in vivo. Adv Funct Mater 23:3488-3493
Arumugam, Thiruvengadam; Ramachandran, Vijaya; Sun, Duoli et al. (2013) Designing and developing S100P inhibitor 5-methyl cromolyn for pancreatic cancer therapy. Mol Cancer Ther 12:654-62

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