Prostate cancer (PCa) has surpassed lung cancer as the leading cancer among American men. The majority of patients have already developed metastatic lesions at initial clinical presentation and androgen ablation has become a standard therapy because PCa is an androgen-dependent (AD) disease. Inevitably, the recurrence of castration resistant PCa (CRPC) will result in mortality of patients since CRPC cells are resistant to conventional chemotherapy. Moreover, because of high age, PCa patients often do not have favorable physical conditions to tolerate undesirable side effects of chemotherapy. Thus, developing a new, safe and effective therapy becomes a high priority. Although PCa patient survival with newly developed therapeutic regimens has been significantly improved, PCa remains incurable. One of the possible theories to explain the recurrence and ineffectiveness of cancer treatment is the cancer stem cell (CSC) model in which a subset of tumor cells is responsible for cancer initiation and progression as well as cancer recurrence. These CSCs share with normal stem cells the properties of self-renewal, immortal and differentiation into a variety of cell types including heterogeneous lineages of cancer cells. Also CSC can re-grow from a few cells left behind after therapy, it will be important to develop therapies that are more specifically directed against CSCs. Thus, targeting cancer stem cell is now becomes an active research area of cancer therapy to achieve the ultimate cure. In order to target PCa specifically, we are developing a new biodegradable and biocompatible nanoparticle that can target PCa specifically with imaging capabilities. Using this unique delivery system, we propose to engineer a unique genotoxin that can preferentially kill PCa cells expressing stem cell properties then evaluate the therapeutic efficacy of PCa monitored by molecular imaging in pre-clinical animal models. We expect be able to monitor the drug delivery and/or response of cancer cells in a real-time manner. This experimental therapy could become a better regimen for treating CRPC because this agent has a PCa specificity, which is expected to be less toxic than chemotherapeutic agents. Most importantly, this proposal is to explore a new avenue of tailored therapy in contrast to conventional therapeutic strategy;we expect that the outcome of this study should have an immediate clinical impact on CRPC therapy.

Public Health Relevance

This project is to explore a new therapeutic strategy for castration resistant prostate cancer (CRPC) by combining a unique therapeutic agent with cancer-specific molecule using a new platform of nanoparticle equipped with imaging capabilities. We will also investigate the mechanism of action of this agent in killing cancer stem cell population. Overall, this outcome of this experimental therapy study using clinical relevant models will provide a new avenue of personalized medicine in CRPC therapy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Developmental Therapeutics Study Section (DT)
Program Officer
Arya, Suresh
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
Zip Code
Li, Juan; Tian, Yuchen; Shan, Dingying et al. (2017) Neuropeptide Y Y1 receptor-mediated biodegradable photoluminescent nanobubbles as ultrasound contrast agents for targeted breast cancer imaging. Biomaterials 116:106-117
Xie, Zhiwei; Su, Yixue; Kim, Gloria B et al. (2017) Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery. Small 13:
Kim, Jimin P; Xie, Zhiwei; Creer, Michael et al. (2017) Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of Cystic Fibrosis. Chem Sci 8:550-558
Xie, Zhiwei; Kim, Jimin P; Cai, Qing et al. (2017) Synthesis and characterization of citrate-based fluorescent small molecules and biodegradable polymers. Acta Biomater 50:361-369
Lin, Hwai-Jeng; Liu, Hsin-Ho; Lin, Chia-Der et al. (2017) Cytolethal Distending Toxin Enhances Radiosensitivity in Prostate Cancer Cells by Regulating Autophagy. Front Cell Infect Microbiol 7:223
Guo, Jinshan; Kim, Gloria B; Shan, Dingying et al. (2017) Click chemistry improved wet adhesion strength of mussel-inspired citrate-based antimicrobial bioadhesives. Biomaterials 112:275-286
Hu, Jianqing; Guo, Jinshan; Xie, Zhiwei et al. (2016) Fluorescence imaging enabled poly(lactide-co-glycolide). Acta Biomater 29:307-319
Kalaba, Surge; Gerhard, Ethan; Winder, Joshua S et al. (2016) Design Strategies and Applications of Biomaterials and Devices for Hernia Repair. Bioact Mater 1:2-17
Yun, Eun-Jin; Zhou, Jiancheng; Lin, Chun-Jung et al. (2016) Targeting Cancer Stem Cells in Castration-Resistant Prostate Cancer. Clin Cancer Res 22:670-9
Guo, Jinshan; Wang, Wei; Hu, Jianqing et al. (2016) Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives. Biomaterials 85:204-17

Showing the most recent 10 out of 24 publications