Prostate cancer accounts for 30,000 deaths a year, which make the second cause of male cancer-related deaths in the Unites States. Current strategies to deal with these diseases have several consequences from toxicity due to off-target effects, Cushing's syndrome, and osteoporosis. The long-term goal of my laboratory is to generate an effective therapy for the treatment of prostate cancer based on non-toxic biomaterials Micellar nanoparticles are the standard nanocarriers for drug delivery applications. However, research has shown that elongated nanoparticles present higher circulation times and enhanced binding for cancer cells than their micellar counterparts. The objective of this proposal is to design nanomaterials of diverse morphologies to identify the most effective prostate cancer targeting nanostructure. In order to do this, we will study the link between nanostructure morphology and prostate cancer cells binding. Nanoparticles of diverse shapes (micelles, fibers and ribbons) will be covalently linked to a small molecule that binds the prostate specific membrane antigen (PSMA), a membrane receptor upregulated in prostate cancer. This will allow us to preferentially direct our nanoparticles to the disease and diminish side effects associated with prostate cancer treatments. Given that glucose transporters are overexpressed in prostate cancer, glucose will also be incorporated into the nanostructures to enhance prostate cancer specificity. The project has four major components: first is the synthesis and purifications of peptidic molecules of diverse compositions that can self-assemble in water into nanoparticles. Then, we will characterize the self-assembly properties of the biomaterials and their supramolecular structure using circular dichroism, small-angle X-ray diffraction, transmission electron microscopy, and atomic force microscopy. In addition, we will study their metabolic stability. For the third component, we will assess the binding affinity and cellular uptake of the nanoparticles in prostate cancer cells that are PSMA-positive and PSMA-negative. Finally, we will study their potential as therapeutic agents by encapsulating and delivering paclitaxel. This proposal is highly interdisciplinary, merging materials sciences, chemistry, and cancer biology, to begin exploratory studies on the shape dependency of prostate cancer targeting materials.
Prostate cancer is the second most common cause of male-related cancer deaths in our country. The objective of this work is to create biomaterials made of non-toxic components that can form nanoparticles. The nanoparticles will form different shapes in order to identify a system that can target prostate cancer cells efficiently.
