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You don't have to pay a penny to download the hit game here. We pay for your stories! Email us at tech the-sun. Jump directly to the content. The active molecules can be selected from the group consisting of drugs and fluorophores. Preferably the drugs are selected from the group consisting of doxorubicin and indomethacin. The fluorophore is preferably fluoresceinamine. In a further embodiment, the covalent bond between the nanoparticle and the thermolabile molecule is obtained by the use of a spacer, preferably a spacer with a radius of gyration between 0.
It can be determined experimentally by means of scattering techniques static light scattering, small angle neutron scattering, X-ray scattering. In particular for the purposes of the present invention it is defined by the equation:.
In one embodiment, the polyethylene glycol has a molecular weight which varies between Da and Da, preferably it is , and Da. A further embodiment of the invention furthermore provides the use of the system according to the invention for use as a molecular thermometer with a spatial resolution of less than 0. The thermolabile system of the invention has the following advantages with respect to the known systems: i it works in solutions at very diluted concentrations 5 nM , in which interparticle interactions are minimised and isothermal conditions are guaranteed; ii it is able to measure the temperature at different distances from the surface of the nanoparticle, therefore allowing mapping of the temperature gradient thanks to the bond of the fluorophore-thermolabile molecule group with the nanoparticle via macromolecular spacers for example PEG of different lengths; iii it is able to measure the differences between the temperature of the medium of the system and the local temperature around the nanoparticle for long time intervals, since a state of equilibrium is maintained.
Said measurements are all taken with a spatial resolution of less than 0. According to a third embodiment of the invention, use of the system of the invention for the controlled release of at least one drug is provided. Advantageously, the use of the system of the invention for the controlled release of a drug allows reduction of the mass ratio between the carrier nanoparticle-spacer-thermosensitive molecule system of the drug and the drug itself with respect to the known release systems, allows the transport of both hydrophilic and lipophilic drugs, allows control of release of the drug according to the presence and length of the spacer group and the position of the azo group and, lastly, allows transport and release of different drugs from the same nanoparticle: positioning at different distances from the nanoparticle surface furthermore allows the independent release of each of them.
According to a fourth embodiment of the invention, use of the system of the invention for the treatment of a tumour is provided. Further characteristics of the present invention will become clear from the following description of some merely illustrative and non-limiting examples. All the other reagents and compounds were purchased from Sigma-Aldrich.
The TEM samples were prepared by drop casting of the solution on a carbon-coated copper grid, leaving the solvent to evaporate. For purification of the iron oxide particles from the free reagents after the synthesis, Amicon centrifuge filters 15 ml, molecular cut-off kDa, Millipore were used in a centrifuge at controlled temperature Sigma, PK.
For the ultrapure samples, the free fluorophore or the doxorubicin were removed by double filtering on gel on PD10 desalinization columns GE Healthcare with ice cold Milli-Q water as eluant. The incubation experiments were conducted in a water bath at controlled temperature Memmert.
Separation of the fluorophore released from the particles was obtained with filtering by, centrifugation in Amicon test tubes 0. The fluorescence spectra were recorded with a Cary Eclipse Varian spectrometer in microcuvettes with three quartz windows Hellma. The procedure is shown schematically in FIG. Briefly, mg 2 mmol of Fe 2 O 3 hydrate catalyst grade, mesh , 2. The mixture was degassed under a high vacuum and magnetic excitation for 1 hour.
Said procedure allows crystallization of the hydrolyzed DCC which can be removed by filtration with a paper filter. Triethyl amine 0. Milli-Q water 5 equivalent volumes was added and the two phases were emulsified by light stirring. At this point the oleic acid exchange takes place and the IONP tend to segregate at the water-toluene interface. Acetone approx. The mixture was lightly stirred again to allow emulsification. After separation of the phases, the aqueous phase was collected.
This step was repeated three times. This step was repeated at least five times. The mixture was stirred for 20 minutes at ambient temperature and then cooled rapidly, placing the vial in an ice bath. The release of the fluorophore following application of a magnetic field of mT modulated at a frequency of The detachment of the fluoresceinamine allows reading of the absolute temperature while the PEG chains act as spacers, allowing sub-nanometric resolution of the temperature measurement.
Following application of the magnetic field, the effective local heating can be expressed as the difference LT between the local temperature T local and the global temperature T global temperature of the medium surrounding the nanoparticles at a great distance from their surface which can be measured with a temperature probe immersed in the solution.
To obtain the quantitative correlation between the fluoresceinamine released and the local temperature, the calibration curves at different temperatures and at pre-set time intervals were constructed. Incubation in a water bath ensures a uniform temperature throughout the sample, so that in this case the local temperature is equal to the global temperature. These storage solutions were used for the incubation and the experiments with the alternating magnetic field.
To construct the calibration curves, portions of 0. For each incubation temperature, 3 individual portions were placed in a water bath at controlled temperature for 1 hour. The solutions were then placed in Amicon centrifuge filters 0. In this phase, the fluoresceinamine released was washed by the filter while the IONP were blocked on a cellulose acetate membrane. To collect any fluoresceinamine molecules trapped in the filter, 0. The eluates were collected and kept in the dark before being analysed by fluorescence spectroscopy.
An optical temperature probe was immersed in the solution to measure in real time the macroscopic temperature which remained constant during the entire measurement and equal to the ambient temperature.
Magnetic fields were applied with intensity B 9, 13 or 17 MT for 1 hour and the solutions were then placed on Amicon centrifuge filters 0. The fluoresceinamine released was washed by the filter while the IONP were blocked on a cellulose acetate membrane. For each sample with different PEG molecular weight and each magnetic field intensity B the procedure was repeated twice to triplicate the results.
The eluates of the incubation and the experiments with the magnetic field were analysed by fluorescence spectroscopy. All the samples were recorded the same day to avoid fluctuations in maximum intensity due to the lamps. The instrument was switched on 1 hour before the measurement to stabilise the temperature of the lamps. The emission signals were collected from to nm.
The photoluminescence signal of the samples analysed I max,incubation increases as the temperature increases see FIG. The coefficient of determination R 2 was then measured, i. The values of A, t, R 2 are reported in table 1. The data reported in the table indicate that the decomposition rate of the azo group depends on the molecular weight of the spacer.
With the calibration curves available and measuring the normalised photoluminescence intensity at nm for the samples after exposure to an alternating magnetic field, the local temperature at different distances from the surface of the nanoparticles can be extrapolated with the following formula:.
The intensity of the magnetic field B was modulated by changing the voltage applied to the coil. A magnetic field varying between 9 and 17 mT modulated at a frequency of Download Now.
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