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Cell-mediated Magnetic hyperthermia of preclinical tumors. Quantitative iron estimation in MNP: Ferrozine based colorimetric method Qualitative iron identification in cells: Prussian blue staining, TEM Cell toxicity assays: Trypan blue counting, MTT assay
Using iron nanoparticles (MNPs) to absorb alternating magnetic field (AMF) energy as a method of generating localized hyperthermia has shown potential as a cancer treatment. Many attempts have been made to increase the localization of MNPs, for example by attaching antibodies recognizing tumor-specific epitopes or peptides binding receptors on tumor cells or neovasculature. Several research groups have shown reliable results using tumor homing cells as delivery cells for different therapeutics. Here we hypothesized that tumor homing cells can carry MNPs specifically to the tumor site, and tumor burden will decrease after AMF exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs).We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After AMF exposure, the targeted delivery of MNPs by the NPCs resulted in a significant decrease in tumor size. Second, monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated magnetic hyperthermia we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors. Based on these observations we concluded that development of localized hyperthermia treatment using tumor tropic cells shows promise as a cancer therapy.
Sivasai Balivada†, Rajashekhar Rachakatla†, Matthew T. Basel†, Hongwang Wang‡, Gwi Moon Seo†, Tej B. Shrestha†, Marla Pyle†, Viktor Chikan‡, Stefan H. Bossmann‡, Deryl L. Troyer†
†-Department ofAnatomy & Physiology ‡- Department of Chemistry, Kansas State University
A. Homing of intravenously injected NPCs expressing Gaussialuciferaseto metastatic melanoma. B.Tumor volumes in mice injected with B16-F10 melanoma cells (*p < 0.05) when compared with saline control.
Histological analysis of tissues from mice treated with MNPs and AMF exposure:
Attenuation of Mouse Melanoma by A/C Magnetic Field after Delivery of Bi-Magnetic Nanoparticles by Neural Progenitor Cells
Raja ShekarRachakatla*, Sivasai Balivada*, Gwi-Moon Seo, Carl B. Myers, Hongwang Wang, Thilani N. Samarakoon, Raj Dani, Marla Pyle, Franklin O. Kroh, Brandon Walker, XiaoxuanLeaym, Olga B. Koper, Viktor Chikan, Stefan H. Bossmann, Masaaki Tamura, and Deryl L. Troyer ACS Nano20104 (12), 7093-7104, * co-first authors
Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model
Matthew T. Basel, Sivasai Balivada, Hongwang Wang, Tej B. Shrestha, Gwi Moon Seo, Marla Pyle, GayaniAbayaweera, Raj Dani, Olga B. Koper, Masaaki Tamura, Viktor Chikan, Stefan H. Bossmann, and Deryl L. Troyer Int J Nanomedicine. 2012; 7: 297–306.I
Increase in survival of mice bearing peritoneal pancreatic tumors by AMF after delivery of MNPs by Mo/Ma:
Kaplan-Meier test showed that survival curves were significantly different for the experimental group compared with other groups.(p<0.005)
MNP/AMF treatment mice survived substantially longer, with mice lasting until 33.5 days
Average increase in survival of treatment group is 7 days
Tumor homing cells can carry MNPs specifically to the tumor site, and tumor burden will decrease after AMF exposure
MATERIALS & METHODS
MNPs testing on NPCs in vitro:
MNPs testing on RAW 264.7 Mo/Ma in vitro:
NPCs migration toward mouse melanoma and attenuation of melanoma growth by AMF after delivery of MNPs by NPCs:
Homing studies of PKH26-loaded RAW 264.7 Mo/Ma on disseminated peritoneal pancreatic cancer: