Past Research Projects
Development of DNA-Silicon Nanoparticle Bioconjugates
The utility of nanoparticle platforms for the delivery of encapsulated and conjugated drugs is well known, benefiting from high loading capacities, extended bioavailability and localization to many disease sites. While gold nanoparticles are commonly used, their expense is prohibitive for widespread development. Silicon Nanoparticles (SNPs), conversely, have been shown to have low toxicity and potentially excellent optical properties. In collaboration with the Fink Lab (Tulane, Chemistry) and the Mitchell Lab (Tulane, Chemical Engineering) who have developed a high-energy ball milling approach for the generation of inexpensive (SNPs), we examined methods of conjugating biologically relevant systems (for e.g., DNA) to the surface of alkyne terminated SNPs. Specifically, we examined the viability of conjugating oligodeoxynucleotides (ODNs) to small NHS-ester terminated silicon nanoparticles as the basis for a bio-therapeutic delivery system, as well as the synthetic benefits of using ODN hybridization to increase surface loading of the nanoparticles, as shown in the two figures below.
Evaluation of Small-Molecule EMT Inhibitors for Pulmonary Fibrosis
The Epithelial to Mesenchymal Transition (EMT) is a process by which normal epithelial cells undergo a morphological change to a mesenchymal morphology. This process is implicated in both metastasis in cancer cells, and in the development of pulmonary fibrosis in the lungs. Matrix Metalloprotiens, especially MMP-3, have been implicated in triggering the transition due to its association with remodeling of the extracellular matrix. Accordingly, a small molecule MMP-3 inhibitor was synthesized and tested over a long-term therapy as a means of reversing EMT in human epithelial breast cancer cells (MDA-MB-231), as a precursor to developing both anti-metastatic therapeutics for cancer and pulmonary fibrosis treatments. This project was in collaboration with the Shan Lab at Tulane Medical School
For cell studies, MDA-MB-231 cells were seeded into a 6-well plate at 1x105 cells per well, cultured with 2 mL per well of DMEM with 10% Fetal Bovine Serum and 1% Penicillin/Streptomycin by volume. After a 24 hour period allowing the cells to adhere to the plate, the medium was replaced by fresh medium containing no additives, DMSO, or the small molecule inhibitor. After allowing the cells to grow in this new medium for two days, the cells were sub-cultured into a fresh 6-well plate with clean medium, and the process repeated. This was continued for 6 doses, or 22 days, and the morphological changes were followed via microscopy.
Images of live cell cultures under 20x magnification. A: Control well, Dose 6, Day 1. B: 10-5 M inhibitor, Dose 6, Day 1. C: Control well, Dose 6, Day 2. D: 10-5 M inhibitor, Dose 6, Day 2.