Title: Local treatment of pancreatic cancer with magnetic nanoparticles
Abstract: Background: Magnetic nanoparticles (MNP) may be utilized for hyperthermic and drug delivery treatment of tumors. After being packed in magnetoliposomes with the chemotherapeutic agent, they are injected into a peripheral vein and accumulated at the cancer site with endoscopically placed magnetic field traps. The MNP are heated by an alternating magnetic field and the drug is released locally. This treatment may be used to achieve secondary resectability. For optimization, we analyzed absorption kinetics of human pancreatic cancer cell lines as well as investigated their response to hyperthermia. Methods: MNP were embedded in a phospholipid double layer and labeled by fluorescence. They were incubated with pancreatic cancer cell lines and the absorption was measured by fluorescence microscopy and magnetic particle spectroscopy. An alternating magnetic field was applied and the biological effects of magnetic hyperthermia were studied by clonogenic assays, qPCR as well as western blotting. Results: We found different characteristic saturation concentrations between 30 pg and 90 pg. The MNP were incorporated homogenously within the cell. Magnetic hyperthermia led to significantly reduced colony numbers. We were able to prove oxidative stress. Tumor cells died partially due to apoptosis, but also because of necroptosis. Conclusion: Treatment of pancreatic cancer with magnetic drug targeting and hyperthermia is possible. Future experiments must investigate these results in animal models.