Hongwang Wang

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.

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.

Ring opening of epoxidized methyl oleate using a novel acid-functionalized iron nanoparticle catalyst

Hydroxyl soybean oils, also called soy polyols, are biobased chemicals designed to replace petroleum-based polyols mainly for polyurethane (PU) applications. Soy polyols are obtained by acid-catalyzed ring opening of expoxidized soybean oils or other epoxidized plant oils by nucleophilic SN2 attack of methanol. Recyclable heterogeneous catalysts are preferred for the ring-opening reactions over non-recyclable homogeneous catalysts because they minimize environmental impact. The drawbacks of current solid catalysts such as SAC 13 and Amberlite 15 are low production yield and high energy consumption. Here, we demonstrate a greener synthetic pathway of soy polyols with low energy consumption and excellent atom economy and environment (E) factor by using novel sulfamic acid-functionalized iron (iron/iron oxide core shell) nanoparticles (NPs) as a heterogeneous catalyst. The excellent selectivity of the reaction with the recyclable NPs was confirmed by 1H NMR, 1H-1H COSY NMR, and ESI-MS comparable to non-recyclable H2SO4. The synthetic route with the NPs resulted in higher product yield (almost 100%) as H2SO4 at room temperature for 30 min over the SAC 13 (83% yield at 60 °C for 60 min) and Amberlite 15 (87% yield at 60 °C for 100 min). Life cycle assessment (LCA) revealed that the NP synthetic technology for soy polyol production is superior or equal to the competing routes (H2SO4, SAC 13, and Amberlite 15 methods) with respect to 9 environmental impacts (acidification potential, ozone depletion potential, smog formation potential, global warming potential, human toxicity by ingestion, human toxicity by inhalation, persistence, bioaccumulation, and abiotic resource depletion potential).

Hexagonal magnetite nanoprisms: preparation, characterization and cellular uptake

The capacity of iron oxide nanocrystals to heat tissue when subjected to an alternating magnetic field (AMF hyperthermia) is shape-selective. Although iron oxide nanostructures with numerous shapes have been synthesized to date, hexagonal Fe3O4 prisms of low toxicity remained elusive. Here, we report the use of a dual ligand system permitting feasible reaction conditions to synthesize nearly perfect hexagonal Fe3O4 nanoplatelet structures, with edge length of 45 ± 5 nm and thickness of 5 to 6 nm. Their Specific Absorption Rate (SAR) is >750 W g(Fe)-1. The Fe3O4 hexagons were coated with a dopamine-based ligand to increase dispersibility in aqueous buffers. The Fe3O4 hexagons were only minimally toxic to RAW264.7 cells, which can be utilized in cell-based cancer targeting approaches.

Effects of storage temperature on airway exosome integrity for diagnostic and functional analyses

ABSTRACT Background: Extracellular vesicles contain biological molecules specified by cell-type of origin and modified by microenvironmental changes. To conduct reproducible studies on exosome content and function, storage conditions need to have minimal impact on airway exosome integrity. Aim: We compared surface properties and protein content of airway exosomes that had been freshly isolated vs. those that had been treated with cold storage or freezing. Methods: Mouse bronchoalveolar lavage fluid (BALF) exosomes purified by differential ultracentrifugation were analysed immediately or stored at +4°C or −80°C. Exosomal structure was assessed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and charge density (zeta potential, ζ). Exosomal protein content, including leaking/dissociating proteins, were identified by label-free LC-MS/MS. Results: Freshly isolated BALF exosomes exhibited a mean diameter of 95 nm and characteristic morphology. Storage had significant impact on BALF exosome size and content. Compared to fresh, exosomes stored at +4°C had a 10% increase in diameter, redistribution to polydisperse aggregates and reduced ζ. Storage at −80°C produced an even greater effect, resulting in a 25% increase in diameter, significantly reducing the ζ, resulting in multilamellar structure formation. In fresh exosomes, we identified 1140 high-confidence proteins enriched in 19 genome ontology biological processes. After storage at room temperature, 848 proteins were identified. In preparations stored at +4°C, 224 proteins appeared in the supernatant fraction compared to the wash fractions from freshly prepared exosomes; these proteins represent exosome leakage or dissociation of loosely bound “peri-exosomal” proteins. In preparations stored at −80°C, 194 proteins appeared in the supernatant fraction, suggesting that distinct protein groups leak from exosomes at different storage temperatures. Conclusions: Storage destabilizes the surface characteristics, morphological features and protein content of BALF exosomes. For preservation of the exosome protein content and representative functional analysis, airway exosomes should be analysed immediately after isolation.

Acid monolayer functionalized iron oxide nanoparticles as catalysts for carbohydrate hydrolysis

Superparamagnetic iron oxide nanoparticles were functionalized with a quasi-monolayer of 11-sulfoundecanoic acid and 10-phosphono-1-decanesulfonic acid ligands to create separable solid acid catalysts. The ligands are bound through carboxylate or phosphonate bonds to the magnetite core. The ligand-core bonding surface is separated by a hydrocarbon linker from an outer surface with exposed sulfonic acid groups. The more tightly packed monolayer of the phosphonate ligand corresponded to a higher sulfonic acid loading by weight, a reduced agglomeration of particles, a greater tendency to remain suspended in solution in the presence of an external magnetic field, and a higher catalytic activity per sulfonic acid group. The particles were characterized by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), potentiometric titration, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), inductively coupled plasma optical emission spectrometry (ICP-OES), and dynamic light scattering (DLS). In sucrose catalysis reactions, the phosphonic–sulfonic nanoparticles (PSNPs) were seen to be incompletely recovered by an external magnetic field, while the carboxylic–sulfonic nanoparticles (CSNPs) showed a trend of increasing activity over the first four recycle runs. The activity of the acid-functionalized nanoparticles was compared to the traditional solid acid catalyst Amberlyst-15 for the hydrolysis of starch in aqueous solution. Catalytic activity for starch hydrolysis was in the order PSNPs > CSNPs > Amberlyst-15. Monolayer acid functionalization of iron oxides presents a novel strategy for the development of recyclable solid acid catalysts.

Carbon dioxide hydrogenation to aromatic hydrocarbons by using an iron/iron oxide nanocatalyst

Summary The quest for renewable and cleaner energy sources to meet the rapid population and economic growth is more urgent than ever before. Being the most abundant carbon source in the atmosphere of Earth, CO2 can be used as an inexpensive C1 building block in the synthesis of aromatic fuels for internal combustion engines. We designed a process capable of synthesizing benzene, toluene, xylenes and mesitylene from CO2 and H2 at modest temperatures (T = 380 to 540 °C) employing Fe/Fe3O4 nanoparticles as catalyst. The synthesis of the catalyst and the mechanism of CO2-hydrogenation will be discussed, as well as further applications of Fe/Fe3O4 nanoparticles in catalysis.

Channel blocking of MspA revisited.

Porin A from Mycobacterium smegmatis (MspA) is a highly stable, octameric channel protein, which acts as the main transporter of electrolytes across the cell membrane. MspA features a narrow, negatively charged constriction zone, allowing stable binding of various analytes thereby blocking the channel. Investigation of channel blocking of mycobacterial porins is of significance in developing alternate treatment methods for tuberculosis. The concept that ruthenium(II)quaterpyridinium complexes have the capability to act as efficient channel blockers for MspA and related porins, emerged after very high binding constants were measured by high-performance liquid chromatography and steady-state luminescence studies. Consequently, the interactions between the ruthenium(II) complex RuC2 molecules and MspA, leading to RuC2@MspA assemblies, have been studied utilizing time-resolved absorption/emission, atomic force microscopy, dynamic light scattering, ζ potential measurements, and isothermal titration calorimetry. The results obtained provide evidence for the formation of clusters/large aggregates of RuC2 and MspA. The results are of interest with respect to utilizing prospective channel blockers in porins. The combination of results from conceptually different techniques shed some light onto the chemical nature of MspA-channel blocker interactions thus contributing to the development of a paradigm for channel blocking.

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.