This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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 drugs 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. Based on these facts, we propose that an instant release of a large amount of drugs into ovarian cancer cells would overwhelm the cancer cells 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.
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