NSF Award
2401938
NON-TECHNICAL SUMMARY:<br/><br/>Prostate cancer is a leading cause of cancer death in men, second only to lung cancer. In the U.S., Black men are 1.7 times as likely to be diagnosed with prostate cancer and more than twice as likely to die from the disease than white men. If caught early enough, a surgeon can remove the area around the tumor site, or more commonly, the entire prostate. Once metastasized, (i.e., spread to other parts of the body), more invasive options may be considered which all have their own side effects. A newer class of cancer therapy that has shown great promise is targeted therapy. While traditional chemotherapy drugs can be harsh on the normal healthy cells leading to considerable side effects, targeted therapy aims to selectively attack the cancer cells based on specific environmental characteristics, thus lowering toxicity to healthy cells. This project explores the preparation of an emerging class of porous materials called metal-organic frameworks (MOFs) which can be used to deliver chemotherapy drugs to precise targets. The overarching goal of this project is to determine how specific structure/property/interactions of MOFs affect their performance in targeted therapies for cancer and related diseases. Curcumin, a natural product derived from the rhizomes of the herb Curcuma longa, commonly known as turmeric, will be the therapeutic drug of focus. Preclinical studies of curcumin have revealed therapeutic properties in a broad range of cancer types. Curcumin-encapsulated MOFs will be decorated with folic acid, which has been shown to target specific cancer cells. Complementary to this work, there will be a focus on engaging undergraduate students of color in research and STEM-focused initiatives that promote social and psychological well-being as well as career and graduate school preparedness.<br/><br/>TECHNICAL SUMMARY:<br/><br/>The overarching goal of this project is to elucidate structure-function relationships of metal-organic frameworks (MOFs) as drug delivery vehicles to inform the rational design of new targeted therapies for cancer and related diseases. While traditional chemotherapy drugs can also be harmful to healthy cells, targeted therapy aims to selectively attack the cancer cells based on specific environmental characteristics, lowering toxicity to healthy cells. These nanomaterials typically consist of at least three components, which are (1) the drug or primary mode of therapy, (2) a vehicle for delivery to targeted sites, and (3) a targeting moiety for selective binding. Curcumin, a naturally derived compound which has demonstrated promising anticancer activity will be explored as the drug of focus. However, it has shown some limitation in clinical efficacy due to low bioavailability and cellular uptake. Encapsulation into porous MOFs will be explored as a mechanism to allow curcumin to selectively pass through the cellular membrane of cancer cells, which based on preclinical data, should significantly increase its efficacy. Due to its discriminate targeting abilities toward folate receptors and prostate-specific membrane antigen, PSMA (receptors upregulated in cancer cells), folic acid will be explored as the targeting agent for the proposed investigation. The main objectives of the project are to (1) investigate the relative curcumin absorption and release behaviors of a highly stable, biocompatible MOF, UiO-66, and a series of its structural analogs and (2) evaluate folic acid-functionalized, curcumin-doped UiO-66 and analogous systems for improved cellular uptake and therapeutic efficacy in prostate cancer cells. Complementary to this work, there will be a focus on engaging undergraduate students of color in research and STEM-focused initiatives. This includes a student mentorship program for first and second-year chemistry students to promoting self-efficacy, career and graduate school preparedness and culturally reflective activities.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
