Preparation Of Hollow-mesoporous M_xFe_3-xO₄?M=Mg,Mn,Fe,Co,Ni,Cu,Zn? Nanoparticles And Research Of Microwave Controlled Drug Release

Varied drug delivery systems have been constructed recently to improve the therapeutic effect of cancer.Efficient drug delivery system should meet the three important requirements of high drug loading capacity,specific drug distribution at tumor sites,and efficient drug release dosage.However,these drug delivery systems always have complex compositions and microstructures,which usually reduce their further drug exploration and clinical application value.While using material that can achieve multiple functions as drug carrier will have brilliant application prospects.Spinel ferrites have high saturation magnetization which can be applied to targeting the loaded anticancer drugs to cancer sites under an external magnetic field,and can transform electromagnetic energy into heat by magnetic loss and dielectric loss.The heat then can be used to weaken or destroy the interaction force between drugs and this carrier,promoting the release of drugs.If the spinel ferrite is designed with mesoporous or hollow-mesoporous nanostructure,its specific surface area and pore volume will be increased to effectively reserve drugs.Therefore,the mesoporous or hollow-mesoporous structured spinel ferrite system is not only simple,but also can achieve the purposes of effective drug loading,magnetic targeting and microwave controlled release.This drug delivery system will contribute to broadening the construction ideas of multi-functional nanocarriers,and also has a great potential for clinical application.Based on the above analysis,this thesis first explored the preparation method of hollow-mesoporous spinel ferrite nanoparticles and synthesized a series of MxFe_3-xO₄?M=Mg,Mn,Fe,Co,Ni,Cu,Zn?.Then the effects of M²⁺ on the morphology and properties of the products were investigated by comparing their mesoporous properties,magnetic properties and microwave-heat transformation performance.Finally,the hollow-mesoporous MxFe_3-xO₄?M=Fe,Co,Zn?nanoparticles with better integrated properties were used as drug carriers to study their loading and microwave controlled release of etoposide?VP 16?.The main research contents and results are as follows:1.Hollow-mesoporous structured CoxFe_3-xO₄ nanoparticles were obtained by CTAB-assisted solvothermal method.It found that the solvothermal temperature,the added contents of CTAB and NaAc have obvious effects on the morphology of CoxFe_3-xO₄.The formation mechanism of hollow-mesoporous structure can be explained by the synergistic effect of CTAB spherical micelles,long-chain CTAB molecules' steric hindrance and Ostwald ripening processes.The prepared CoxFe_3-xO₄ has suitable specific surface area?58.03 m2/g?and pore volume?0.13 cm3/g?for drug loading,high saturation magnetization?74.8 emu/g?for magnetic targeting,and favorable microwave-heat transformation performance?its sodium chloride suspension increased by 24? in 3 min?which can be used for microwave-responsive controllable drug release.2.The NixFe_3-xO₄ and CuxFe_3-xO₄ products prepared by solvothermal method contained Cu and Ni impurities,respectively.The non-magnetic Cu impurities contained in the hollow-mesoporous CuxFe_3-xO₄ can be completely removed by repeated magnetic separation.Increasing the solvothermal temperature,reducing the amount of NaAc or adding a small amount of NO3-can reduce but can not completely avoid the presence of Ni impurities in NixFe_3-xO₄.However,pure mesoporous NixFe_3-xO₄ can be obtained when the nitrates of Fe?and Ni? were used.The surface area of CuxFe_3-xO₄ and NixFe_3-xO₄ nanoparticles are similar?about 59 m/g?,but the pore volume of hollow-mesoporous CuxFe_3-xO₄ is larger.Both of them are paramagnetic,and the Ms value?67.4 emu/g?of CuxFe_3-xO₄ is much higher than that of NixFe_3-xO₄,and the former also has higher microwave-heat transformation performance.3.The mesoporous MgxFe_3-xO₄,MnxFe_3-xO₄,and hollow-mesoporous Fe3O4,ZnxFe_3-xO₄ were synthesized by the same solvothermal method.The BET surface area of all the MxFe_3-xO₄ is 50-60 m2/g,except that the specific surface area of MgxFe_3-xO₄ is slightly larger?106.6 cm3/g?,and the pore volume of hollow-mesoporous MxFe_3-xO₄?M=Fe,Co,Cu,Zn?is larger than that of mesoporous MxFe_3-xO₄?M=Mg,Mn,Ni?.The Ms values sequence of MxFe_3-xO₄ is Fe3O4>CoxFe_3-xO₄= ZnxFe_3-xO₄?MnxFe_3-xO₄>CuxFe_3-xO₄>MgxFe_3-xO₄>NixFe_3-xO₄,and the ferrites are paramagnetic except the ferromagnetic CoxFe_3-xO₄.High Ms value,hysteresis loop area,and hollow-mesoporous structure are favorable for microwave-heat transformation performance,and that of CoxFe_3-xO₄ is the best.MxFe_3-xO₄?M=Fe,Co,Zn?nanoparticles with better integrated performances were used as drug carriers of VP 16,and the results inform that the loading efficiencies of Fe3O4 and CoxFe_3-xO₄ were 61.5%and 64.8%,higher than that of ZnxFe_3-xO₄.Under microwave irradiation,both of drug release rate?69.1%?and release content?8.5 mg?of CoxFe_3-xO₄ nanocarriers were the highest,achieving the best microwave controlled drug release.In this paper,a series of spinel ferrites with hollow-mesoporous structure were prepared,and their composition and preparation conditions were optimized.It was proved that the simple CoxFe_3-xO₄ carrier has better integrated performances of drug-loading,magnetic targeting and controllable release,which lay a theoretical foundation to promote further clinical application of the targeted controllable drug delivery system.