The research work has focused on innovative hybrid multiscale devices for theranostics and the engineering of functional DNA systems with potential in oncology. This includes:
1. The development of novel cancer therapeutics based on tumor-targeting, microRNA-silencing porous silicon nanoparticles (pSiNPs). We focused on ovarian cancer, which is the most lethal gynecologic malignancy and one of the leading causes of cancer mortality among women, and set out to target miR-21, which is associated with cell proliferation, multidrug resistance, and tumor invasion. We engineered tumor-targeting, anti-miR nanotherapeutics that provided anticancer activity in a mouse model of ovarian cancer. Porous silicon nanoparticles are loaded with an artificial oligonucleotide, a locked nucleic acid (LNA), targeting miR-21, and decorated with a tumor-homing peptide that allows for enhanced accumulation in the tumor microenvironment. After testing in a xenograft mouse model of ovarian cancer developed from human COV-318 cells, we were able to silence miR-21 and achieved complete inhibition of tumor growth with no side effects. We observed no increase of tumor volume over the course of a 10-day treatment. The work has been published in ACS Appl. Mater. Interfaces 2019, 11, 27, 23926-23937.
2. The fabrication of a nano-in-nano platform housing miRNA-responsive dynamic DNA nanodevices incorporated into a hybrid polymer/porous silicon scaffold for sensing of miRNA markers in situ and in real time. . We demonstrated long-term release of the engineered DNA payload with retention of specificity and functionality over 20 days. This suggests that extracellular miRNA markers may be detected in cell culture over several weeks, providing a new means for real-time monitoring of disease conditions. The research has recently led to a publication in Nanoscale, 2020,12, 2333-2339.
3. The manufacturing of tissue engineering scaffolds made from biocompatible polymers aimed to provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. This has been accomplished by including neurotrophic payloads in the scaffold to substantially enhance regrowth and repair processes. We have tested three different therapeutic payloads, a protein, a small molecule and and an RNA aptamer. Each therapeutic was loaded using a tailor loading chemistry that is optimized to slow the rate of release of these water-soluble payloads.The nanofiber hybrids were demonstrated to increase neurite extension in a dorsal root ganglion explant assay. A manuscript based on this work is currently under review.
4. The design of programmable DNA-based transducers responding to biomolecular inputs for the actuation of synthetic theranostic molecular networks. This has been carried out by designing, developing and testing nucleic acid based-networks controlled by oncogenic transcription factors through specific DNA actuators. The main goal is to craft novel oncogenic TF-controlled molecular technologies with potential in precision oncology.
