Anti-pancreatic Cancer Effects of Novel Artemisinin-containing Nanogels

Abstract

Pancreatic cancer has a 12% five-year survival rate in the United States, making it the fourth deadliest cancer. Current treatment options include chemotherapy with and without radiation therapy, targeted therapy, or surgery; however, these options have limited success due to low efficiency and adverse effects. In this research, we investigate the efficiency of a proprietary technology NanoART631 (PCT/US2023/019974) invented by our advisor Dr. Tao Lowe and her collaborator Dr. Curt Civin in treating pancreatic cancer. NanoART631 is a nanogel system composed of thermoresponsive poly (N-isopropylacrylamide) and biodegradable dextran-lactate-2-hydroxyethyl-methacrylate, encapsulated with an artemisinin (ART) dimer with a molecular weight of 631 Da. NanoART631 previously demonstrated effective killing of human leukemia cells and sustained the release of ART631 for more than one month in the Lowe lab. However, NanoART631 has not been tested in regard to pancreatic cancer. In our study, we used Fourier transform infrared spectra (FTIR) to characterize the chemical structures of NanoART631s containing different amounts of ART631: 0, 2, 5 and 10 wt%. We also used Zetasizer Ultra to characterize the hydrodynamic particle size, polydispersity index (PDI) and zeta-potential of NanoART631s in water and two culture media for human pancreatic PANC-1 and MiaPaCa2 cells. The results showed that NanoART631s were monodisperse with hydrodynamic diameters between 100 and 230 nm and PDI <0.25 at 37 oC and both the cell culture media decreased the particle size and there was no difference of the effects of the two cell culture media on the particle size. The magnitudes of the zeta potential of 0, 2, 5 and 10 wt% NanoART631 in water at both room and body temperature were consistently below 20 mV. In both cell mediums at body temperature, the magnitudes of the zeta potential of 0, 2, 5 and 10 wt% NanoART631 were consistently below 5mV. We additionally used MTT assay to study the cytotoxicity of NanoART631s to PANC-1 and MiaPaCa2 cells as a function of concentration and determined the effectiveness of NanoART631s in killing the two cells by calculating their IC50s. The IC50s of NanoART631s containing 2, 5 and 10 wt% ART631 were between 20 and 200 nM depending on the cell type. The effectiveness of killing the both human pancreatic cancer cells increased with increasing the amount of ART631 in the nanoparticles. The NanoART631s have potential as an effective novel therapy to treat pancreatic as well as many other cancers.