| Due to the good biocompatibility and the satisfactory chemical stability, the nano-particles have been widely used in the field of biomedicine. Especially, they are often used in cellular labeling and magnetic separation, MRI contrast agent, drug delivery agents, tumor thermotherapy and so on. However how to increase the magnetic performance and drug-loading capacity, and how to achieve MNPs-based targeted drug delivery and effective imaging with99Tcm-labelled are the main problem that researches facing.In this thesis, magnetic nano particles (MNPs) and dopped MNPs with excellent magnetic performance were synthesized by solvothermal method, coprecipitation method and reflux method, with FeCl3·6H2O and FeCl2·4H2O used as iron sources, anhydrous rare earth chloride and non-magnetic ion formate containing hydrazine as doping source respectively. The MNPs can be used for Mitomycin C drug loading, radioactive elements (99Tcm) labeling and In-vivo SPECT imaging, as well as application of magnetic targeting in humans. This thesis contains the following works:First, the amino-functionalized MNPs@SiO2core/shell nanoparticles with high dispersibility were synthesized by solvothermal method, and the doping of Eu+and Sm3+into nano Fe3O4was studied. The results show that Eu ions had doped in the Fe3O4cell in mixed-valence of Eu3+/Eu2+, the doping could change morphologies and magnetic properties of the Fe3O4cell. When the Eu and Sm doping amount were increased, the doped Fe3O4nanoparticles changed from hollow nanospheres into spherical particles, and finally changed into uniform cube-shaped particles with13nm in diameter, resulting in change of shape anisotropy, which may affect their coercivity and saturation magnetization. It was found that higher Sm3+-doping amount led to stronger magnetic dipole transitions, while the Eun+-doping amount had little effect on the magnetic dipole transitions, thus resulting in different changes in their saturation magnetization with doping amount.Second, Fe3O4magnetic nanoparticles with uniform particle size about20nm were prepared by co-precipitation method with tetramethyl ammonium hydroxide (TMAH) as precipitant and dispersing agent. Then the as-synthesized Fe3O4particles were first taken to react with non-magnetic ion (magnesium or aluminum ion) formate containing hydrazine at2%～10%molar doping ratio to prepare strong magnetic non-magnetic ion dopped MNPs by solid-solid reaction. Their saturation magnetization (Ms) was determined by vibrating sample magnetometer (VSM), the changes of Ms with Mg2+and Al3+doping amount was also studied. By analysis of the magnetic Mossbauer spectra of non-magnetic ion dopped MNPs, the ratio of the relative population of A-site Fe atoms to B-site Fe atoms in the inverse spinel structure of Fe3O4was studied. The reason why Ms changed after doping Mg2+and Al3+can be explained by considering the VSM determination results and changes of unit-cell parameters obtained from the indexing of the experimental XRD pattern. Moreover, the targeting performance of MNPs at magnetic targeting interfered sites was studied by capillary simulating vein, and spherical glass balls simulating perivascular tumor tissue also.Third, based on the fact that long alkyl chain trimethoxysilane has the characteristic of being easily hydrolysized and condensed into polysiloxane, the α-Fe2O3@SiO2composite particles were synthesized by a modified StOber method, and further covered by mesoporous mSiO2on their surface with different structure through adjusting alcohol/water ratio and chain-length of long alkyl chain trimethoxysilane. Finally, the magnetic hollow spheres (HMNPs-Cn, n=16,18) with different pore diameter and cavity volume were obtained by using selective etching technique to treat Fe3O4@SiO2@mSiO2. In this thesis, the loading and release kinetics of mitomycin C (MMC) on HMNPs-C18and HMNPs-C16were studied, the results showed, HMNPs-C18has a higher drug loading than HMNPs-C16, both of them have different drug release kinetics model for MMC, due to their different pore diameter and cavity volume. Besides, the labeling of radioactive element99Tcm by HMNPs-C18was also studied.Fourth, the solvothermal method, TMAH coprecipitation method and reflux method were employed to prepare MNPs respectively. After that, the MNPs@SiO2-NH-DTPAA (un-labeled compound) with DTPAA monoanhydride was prepared successively with the following procedures on the MNPs surface:(a) Sol-Gel process,(b) surface amination process and (c) equimolar coupling of c-DTPAA bis-anhydride on the surface of amino-functionalized nano magnetic particles. Among these un-labeled compounds, the Al3’ion dopped MNPs@SiO2-NH-DTPAA prepared by TMAH coprecipitation and following Al3+doping, solid-solid reaction was screened out to have the highest saturation magnetization (65.7emu/g), and labeling efficiency (93.2%).In this thesis, Tumor-Free New Zealand white rabbit and Leg-VX2Tumor-Bearing New Zealand white rabbit were selected as experimental animal model, which are all treated by the injection of labeled compound in one ear vein, after that, the SPECT images were obtained from two-dimensional static images respectively. Based on the information from the images, the natural distribution and magnetic targeting distribution were first studied. Semiquantitative analysis can be achieved by calculation of region of interest ratios (ROI) using liver or lung for comparison, and according to the semiquantitative analysis, in vivo radioactivity count ratio of magnetic targeting interfered lesion’s site to non-interfered lesion’s site was calculated to evaluate in vivo targeting effects of labeled compound in Tumor-Bearing New Zealand white rabbit. The results will offer important references for magnetic targeting drug-loaded system.Fifth, by reaction of glutaric anhydride with an active imino group in mitomycin C (MMC), the MMC-glutaric acid derivatives can be prepared. Then the obtained products underwent esterification with N-hydroxysuccinimide (NHS) followed by passing them through a column of dextran gel to isolate and purify the activated ester of glutaric MMC.On the other hand, Ald-Fe3O4@SiO2-NH2composite particles with high saturation magnetization were prepared successively with the procedures:(a) non-magnetic ion doping, solid-solid reaction,(b) Sol-Gel process and (c) surface amination process.In this thesis, by first coupling the activated ester of glutaric MMC with the amino-functionalized Ald-Fe3O4@SiO2-NH2composite particles in the1,2-dimethoxyethane, the MMC grafted Ald-Fe3O4@SiO2-NH2composite particles were further prepared, which provides reference of the route for preparing this targeted drugs. The targeting compounds were demonstrated by nuclear magnetic resonance (NMR) spectra, elemental analysis, UV and FT-IR spectra. |
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