Preparation Of Magnetic Nanomaterials By Microwave Approach And Their Applications In Transcatheter Arterail Embolizaton Hyperthemia

Recently,functional magnetite(Fe3O4)nanomaterials have been widely used in biomedical applications with outstanding achievements,such as tumor magnetic induction hyperthermia,magnetic resonance imaging(MRI),immunoassay and targeted drug delivery.Hence,how to achieve the optimal control preparation and clinical application has become the goal of scientific researchers.Currently,the thermal decomposition technique largely received a high reputation to the preparation of high-quality magnetic NPs with well-defined morphologies and narrow size distributions,however,the ineludible problems during the synthetic process(ie.thermal gradient,harsh reaction condition and high energy consumption,etc.)had hindered thermal decomposition for further application.Therefore,to develop the more suitable synthesis approach to handle with the bottleneck of thermal decomposition,then to study the preparation mechanism and eventually to improve the performance for realizing the aim of clinical applications has become one of the most challenging projects in this field.We take advantage of microwave technique for approach innovation.High boiling point solvent was chosen to be reaction medium and acetylacetone iron was as precursor,respectively.As a result,monodisperse Fe3O4 NPs(a yield of 90.1%)were obtained with low energy consumption.In terms of microwave heating experiments,vector network analyzer and Raman real-time tracking to investigate the fabrication mechanism,we confirmed for the first time that NPs in microwave preparation process can effectively absorb electromagnetic energy and synchronously convert into thermal energy to promote NPs growth.It was found that the "internal heating" behavior caused by microwave with high efficiency,which can not only eliminate the thermal gradient during thereaction process,but also to achieve the rapid and stable preparation with low energy consumption.Meanwhile,this study provides insight to the preparation mechanism of microwave-assisted thermal decomposition and is expected to achieve the controllable scale-up production by multimode microwave reactorIn addition,the size of NPs is a key factor for determining their electromagnetic properties.For this purpose,we focus on the size dependent magneto-thermal behavior under alternating magnetic field(AMF)as well as the microwave absorption performance.We then prepared 4 different sizes of NPs which from single domain to multidomain(4 nm,20 nm,50 nm,200 nm)by microwave assisted thermal decomposition,and investigated their size-dependent electromagnetic properties at AMF frequency(390 kHz&780 kHz)and microwave frequency(2-18 GHz).Results showed that the NPs with single domain size of 20 nm possess maximum SAR value in AMF while the RL value increases with the size at microwave frequency.To insightfully understand the microwave absorbing regular pattern on size effect,Object Oriented MicroMagnetic Framework(OOMMF)simulation was performed.It was found that the coupling between NPs and electromagnetic field,and the dipole interaction between NPs would effectively affect the microwave absorption behavior.This work provides a valuable reference for clinical application of microwave hyperthermia.To further promote clinical application,we developed a strategy which combined transcatheter arterial embolization with magnetic hyperthermia(TAEMH)for hepatocellular carcinoma(HCC)therapy.Firstly,the PLGA magnetic microspheres(MMs)with adjustable size range(100 to 1000 ?m)were prepared via rapid membrane emulsification platform.After performing a series of in vitro characterization of PLGA-MMs,We then cooperated with Jiangsu Cancer Hospital to systematically evaluate the therapeutic effect of TAEMH.The VX2 orthotopic hepatocarcinoma models were established for in vivo evaluation.Experimental results demonstrated that while exposed to alternating magnetic field(AMF)after TAE,the tumor edge could be heated up by more than 15?both in vivo and in vitro,whereas only a negligible increase of temperature was observed in the normal hepatic parenchyma(NHP)nearby.Sufficient temperature increase induces apoptosis of tumor cells.This can further inhibit the tumor angiogenesis and results in necrosis compared to the rabbits only treated with TAE.In stark contrast,tumors rapidly grow and subtotal metastasis occurs in the lungs or kidneys causing severe complications for rabbits which are only irradiated under AMF.Importantly,the tumor related markers expression(VEGF,p53,ALDHLA1)and the biochemical criterion,as well as the pathological section were detected.Results further confirmed that the treatment protocol using PLGA-MMs could achieve good biosafety and excellent therapeutic efficacy,which are promising for liver cancer therapy in the future.