This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ovarian cancer continues to be a major life-threatening disease for women. Unfortunately, it responds only moderately to the current standard chemotherapy. The underlying reason for its insensitivity to chemotherapy is that ovarian cancer cells have many defense mechanisms to resist drug actions. Especially, they can effectively reduce the cell drug concentration by slowing the drug?s entry into the cells, removing drugs out of the cells, and converting drugs into harmless forms. As a result, the drug concentration in cancer cells is too low to effectively kill them. More importantly, cancer cells surviving this low drug concentration are induced to become more insensitive to drugs, causing treatment failure. Based on these facts, we propose that an instant release of a large amount of drugs into ovarian cancer cells would overwhelm the cancer cell?s defense mechanisms and build up a cell drug concentration much higher than the cell-killing threshold, and thus effectively kill the ovarian cancer cells. To test this hypothesis, the objective of the project is to develop and evaluate ovarian cancer-targeted and-activated instant-intracellular-drug-release (IIDR) nanoparticles for ovarian cancer chemotherapy. The designed IIDR nanoparticle can specifically accumulate in ovarian cancer tissues, enter the cancer cells effectively via several mechanisms, and instantly dump the drug into the cells. The resultant high drug concentration leads to effective cell-killing. Potential outcomes and benefits of the research: The proposed IIDR is an innovative means to overcome cancer?s insensitivity to drugs to enhance the therapeutic efficacy of ovarian cancer treatment. We expect that the IIDR nanoparticles are also versatile for the treatment of different types of ovarian cancer because they are designed to enter cancer cells via a universal mechanism. In addition, the side effects of this treatment should be substantially reduced compared to the conventional dosage form of cancer chemotherapy because the nanoparticles preferentially penetrate inside cancer cells and release drugs there. Thus, the results will not only provide an effective new cancer therapeutic strategy but will also advance our understanding of how to improve ovarian cancer chemotherapy with targeted drug delivery via smart nanocarriers.
Showing the most recent 10 out of 325 publications
