Olga Koper

A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles: a mouse study

BackgroundThere is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy.MethodsThe influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands.ResultsThe magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection.ConclusionsThese results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art.

Nanoscale Powders and Formulations with Biocidal Activity Toward Spores and Vegetative Cells of Bacillus Species, Viruses, and Toxins

Certain formulations of nanoscale powders possess antimicrobial properties. These formulations are made of simple, nontoxic metal oxides such as magnesium oxide (MgO) and calcium oxide (CaO, lime) in nanocrystalline form, carrying active forms of halogens, for example, MgO · Cl2 and MgO · Br2. When these ultrafine powders contact vegetative cells of Escherichia coli, Bacillus cereus, or Bacillus globigii, over 90% are killed within a few minutes. Likewise, spore forms of the Bacillus species are decontaminated within several hours. Dry contact with aflatoxins and contact with MS2 bacteriophage (surrogate of human enterovirus) in water also causes decontamination in minutes.

Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model

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.

Attenuation of Mouse Melanoma by A/C Magnetic Field after Delivery of Bi-Magnetic Nanoparticles by Neural Progenitor Cells

Localized magnetic hyperthermia as a treatment modality for cancer has generated renewed interest, particularly if it can be targeted to the tumor site. We examined whether tumor-tropic neural progenitor cells (NPCs) could be utilized as cell delivery vehicles for achieving preferential accumulation of core/shell iron/iron oxide magnetic nanoparticles (MNPs) within a mouse model of melanoma. We developed aminosiloxane-porphyrin functionalized MNPs, evaluated cell viability and loading efficiency, and transplanted neural progenitor cells loaded with this cargo into mice with melanoma. NPCs were efficiently loaded with core/shell Fe/Fe(3)O(4) MNPs with minimal cytotoxicity; the MNPs accumulated as aggregates in the cytosol. The NPCs loaded with MNPs could travel to subcutaneous melanomas, and after A/C (alternating current) magnetic field (AMF) exposure, the targeted delivery of MNPs by the cells resulted in a measurable regression of the tumors. The tumor attenuation was significant (p < 0.05) a short time (24 h) after the last of three AMF exposures.

Synthesis of carbon-coated MgO nanoparticles

Carbon-coated MgO nanoparticles, with carbon forming a porous coating on the surface of MgO nanoparticles, have been prepared by two different techniques. Resorcinol has been found to be an efficient agent for the modification of magnesium methoxide leading to carbon-coated MgO nanocrystals of small crystallite size and high surface area. Decomposition of dry magnesium methoxide under an inert gas flow proved to be another efficient and economical way to synthesise carbon-coated MgO. The carbon coating acts as a hydrophobic barrier partially protecting the core metal oxide from water adsorption and conversion to magnesium hydroxide. However, destructive adsorption reactions can still proceed on the metal oxide surface, as evidenced by the dehydrochlorination of 2-chloroethyl ethyl sulfide (2-CEES) and 1-chlorobutane. The overall stability of the material in the presence of water vapor is significantly improved in comparison with non-coated nanocrystalline MgO.

Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection.

Summary Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.

Nanoscale Metal Oxides as Destructive Adsorbents. New Surface Chemistry and Environmental Applications

An aerogel procedure combined with hypercritical drying has yielded magnesium oxide and calcium oxide in ultrahigh surface area forms. These nanoparticles of MgO and CaO possess intrinsically higher surface reactivities, and serve as destructive adsorbents for a variety of toxic substances, including organophosphorus compounds, and chlorocarbons. They also serve to adsorb large amounts of gases very strongly, such as CO2, SO2, SO3, and HX. A second generation of even more effective destructive adsorbents has been prepared by depositing a monolayer of transition metal oxide on the MgO or CaO nanoparticles, for example [Fe2O3]MgO, [NiO]CaO, [ZnO]MgO, and others. As a test reaction CCl4 + [Fe2O3]MgO→ [FeClx]MgCl2 + CO2 was employed. This gassolid reaction was facilitated and enhanced by two things: (1) Unusual morphology of nanoscale MgO, probably because of exposure of {111} crystal faces and high concentrations of edge sites and defect sites, and (2) the presence of the thin layer of Fe2O3 (or other transition metal oxide), which allows a catalytic O2-/Cl- solid state ion/ion exchange to take place. The reaction proceeded to almost stoichiometric proportions when Fe2O3 was present, which indicates that the surface Fe2O3-FeC1x layer is mobile and dynamic, allowing continual O2-/C1- exchange deeper into the nanoparticle. Morphological studies were aided by Atomic Force Microscopy experiments, which will also be discussed.