Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.
We have transfected murine neural stem cells (NSCs) with a plasmid expressing Gaussia luciferase (gLuc). The enzyme is secreted from the cells. We have used the gLuc-containing supernatant from cultured NSCs to perform in vitro photodynamic therapy of murine melanoma cells (B16F10). The treatment system was comprised of 5-aminolevulinic acid as a prodrug for the synthesis of the 10 photosensitizer protoporphyrin IX, Gaussia luciferase, and its substrate, coelenterazine. A significant reduction in the number of live melanoma cells was observed 36h after coelenterazine-mediated PDT.
Objectives: To isolate and maintain canine Wharton's jelly mesenchymal stromal cells (WJMSC) in culture, determine the effects of micellar nanoparticles containing doxorubicin (DOX) on WJMSC and canine osteosarcoma (OSA) D17 cells, and determine the effects of WJMSC loaded with micellar nanoparticles containing DOX on OSA D17 cell viability.Procedures: Stromal cells were isolated from canine umbilical cords. Micellar nanoparticles containing DOX were prepared and added to individual culture plates containing canine WJMSC and OSA D17 cells to determine DOX in micelles (DOX-M) effects on cell growth and viability. Conditioned media (CM) from culture plates containing canine WJMSC incubated with various DOX-M concentrations was added to OSA D17 cells. An MTT assay was performed to assess osteosarcoma D17 cell viability. A trypan blue stain was utilized to perform cell counts to determine the effect of the DOX-M on WJMSC growth.Results: WJMSC were successfully isolated and maintained in culture. Micellar nanoparticles containing DOX decreased viability of OSA D17 cells. Osteosarcoma D17 cell viability decreased following incubation with CM obtained from WJMSC loaded with DOX-M. Significant decreases in OSA D17 cell viability were observed after incubation with the CM of canine WJMSC loaded with 10 μM DOX-M at 96 hours (p=0.0037). Significant decreases were also observed with the CM from WJMSC loaded with 1 μM DOX-M at 96 hours (p=0.0222). WJMSC numbers decreased in a dose dependent manner following incubation with DOX-M. The decrease in WJMSC number was not secondary to cytotoxicity as all variables produced similar percentages of dead WJMSC.
Conclusions:Canine WJMSC can be isolated and maintained in culture. DOX-M produces OSA D17 cytotoxicity and slows proliferation of canine WJMSC. WJMSC containing DOX-M cause OSA D17 cell cytotoxicity. These data support in vivo experiments utilizing canine WJMSC and micellar nanoparticles.
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