|Anh Nguyen, 1st Year
Program: Chemical Engineering
Advisor: Ashish Kulkarni
Education: B.S. in Chemistry, Murray State University, Murray, KY (2013-2017)
Cancer is one of the leading causes of death worldwide and has a large negative impact on society. According to the American Cancer Society, there will be approximately 1.7 million new cases of cancer and 600,000 cases of cancer-related death in the United States in 2018. During the process of tumor development, the body’s immune system mounts a defense against these cancerous cells to inhibit their growth. However, elimination of cancer is often hindered not only because of the uncontrollable metastasis of tumor cells, but also because these malignant tumor cells can develop various immune escape mechanisms. To help restrain the immune escape, immunotherapy became a powerful tool for cancer treatment. One important breakthrough in immunotherapy is the discovery of immune checkpoint inhibitors (e.g., anti PD-1, anti PD-L1, anti CTLA-4), which stop cancer cells from escaping immune attacks. However, constant interactions with immune system during therapy can cause tumor to recruit other evasion pathways such as hiding their antigens, employing immunosuppressive cells, etc., which consequently induce the resistance to immunotherapy drugs. Besides the resistance to treatment, multiple side effects were reported to attribute to immunotherapeutics that significantly impact patients’ lives. Therefore, it is essential to discover an early-stage detecting method to identify responding patients, so as to alternate the treatment before the patients have to suffer any further harm.
The conventional imaging techniques such as MRI or PET/CT scanning can only visualize the changes in tumor volume, which takes longer time to occur, and in some cases can be misclassified as pseudo-progression. In order to monitor the treatment efficacy at sooner stage, we focus on developing a nanotheranostic system that can self-report the cellular activities during the apoptosis process of cancer cells. The self-stimuli reporter nanoparticles can co-deliver an immunotherapeutic agent and an enzyme-responsive fluorescent probe. This idea utilizes aggregation-caused quenching (ACQ) where a donor-acceptor pair in transferring energy through a non-radiative process. By attaching this quencher-fluorescence pair to an enzyme responsive peptide sequence, we aim to study the biological activities occurring at cellular and molecular level during apoptosis caused by immunotherapy. The imaging probe is delivered to tumor cells using polymeric nanoparticles, together with immunotherapeutic agent. Our studies show that this polymeric nano-carrier was capable of monitoring in real time the apoptotic process when C57BL/6 mice were treated with either chemotherapeutic drug (paclitaxel) or immunotherapeutic drug (immune checkpoint inhibitor).
Another goal in our study is to develop the early monitoring of anticancer treatment efficacy to a more powerful system using magnetic resonance imaging (MRI). We are currently engineering a nanoparticle that can deliver an activatable 19F-based MRI probe to tumor site. MRI imaging work will be collaborated with Radiology department from UMass Medical school and Brigham and Women’s hospital. With this idea, we can overcome the limitation of low tissue-penetration of fluorophore spectrum. Using radio-contrasting agents allows a potential future translation into clinical trial, providing patients a much earlier answer of their treatment efficacy that can have a great impact on their quality of life.
- Nguyen, A., Rhoades, T. C., Johnson, R. D. & Miller, K. M. Influence of Anion and Crosslink Density on the Ionic Conductivity of 1,2,3-Triazolium-Based Poly(ionic liquid) Polyester Networks. Macromolecular Chemistry and Physics 218, (2017).
- Tracy, C. A., Adler, A. M., Nguyen, A., Johnson, R. D. & Miller, K. M. Covalently Crosslinked 1,2,3-Triazolium-Containing Polyester Networks: Thermal, Mechanical, and Conductive Properties. ACS Omega 3, 13442–13453 (2018).