(4cd) Leveraging Electrostatic Interactions to Enhance Drug Delivery through Tumor Extracellular Matrix

During my Ph.D., I have made significant contributions to understand how electrostatic interactions between nanoscale carriers and tumor extracellular matrix (ECM) impact transport and how these interactions can be harnessed to improve intratumoral transport. Tumor ECM is known to be a crucial interaction barrier that prevents effective drug transport and delivery. Using high-throughput techniques, such as phage display and next-generation sequencing, I identified peptides to improve the transport of therapeutics in the cancer environment (Nanoscale, 2019). Contrary to current dogma, I have demonstrated that positively charged surfaces (i.e., peptide coated surfaces) that achieve weak and reversible electrostatic interactions with the tumor ECM exhibit improved uptake, retention, and penetration compared to their neutrally charged counterparts (Acta Biomaterialia, 2020).

Leveraging my findings, I am finishing my doctoral studies to show that cationic peptides can enhance intratumoral transport and the antitumor efficacy of immune checkpoint blockade antibodies (ICBs) using a murine melanoma model. I found that the cationic peptide electrostatically interacted with the net negatively charged tumor ECM and enhanced the tumor tissue binding of the ICBs. Therefore, the ICBs were retained longer in the tumor environment. The longer retention of the ICBs recruited a higher number of activated tumor-infiltrating T-cells and significantly depleted regulatory T-cells in the tumor and tumor-draining lymph nodes, resulting in delayed tumor growth.

Research Interests

From my work with cell culture, ex vivo tissue culture, and animal model development, I have realized there is an unmet gap to develop models that can more easily recapitulate the dynamic and transport features of disease environments. I believe that engineering 3D organoid cultures will more accurately reflect the physiological disease environment, and further incorporating these organoids in organ-on-a-chip systems will provide high throughput platforms for rapid drug discovery and personalized medicines. I would be enthusiastic to complete my postdoctoral training in designing 3D models that better reflect various disease environments to accelerate the progress of drug discovery.