The Preparation Of Magnetic Responsive Plga Microsphere And Their Fundamental Research In Application Of Chemo-thermal Therapy

Cancer has become one of the major diseases threatening human health becauseof low cure rate,high recurrence rate and fatality rate.Scientists have been committed to develop efficient methods for cancer treatment.The hyperthermia and chemotherapy therapeutic functions are combined in the same nanosystem taking advantage of the great potential of hyperthermia and controlled drug delivery in the treatment of cancer,and also benefiting from the synergetic effect of the combined therapy.Therefore,development of effective strategies to treat cancer combining small side effects of hyperthermia therapy with the high efficiency of chemotherapy drugs becomes aresearch focus.Magnetic iron oxide nanoparticles(IOs)with high performance is of great scientific interest for researchers from a wide range of biomedicine applications,including magnetic resonance imaging(MRI),cancer magnetic hyperthermia and controlled drug delivery.Due to the non-toxic and biocompatible,PLGA is used in the sustained release or controlled release system.However,the release of drug molecules from a PLGA-based carrier is usually a slow process due to degradation and diffusion mechanisms,and the low concentration drug release may result in the multidrug resistance(MDR).Therefore,modulating the drug release kinetics of PLGA-based drug delivery carries is vital for maximizing their efficacy to tumors therapy.Herein,we developed doxorubicin-loaded magnetic PLGA microspheres,in which DOX was encapsulated in the core and γ-Fe2O3@DMSA nanoparticles were electrostatically assembled on the surface of microsphere.The combination of hyperthermia and chemotherapy can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.The major works of thesis are as follows:1.The preparation of magnetic response PLGA microspheres and their application in thermal-chemotherapyFirstly,the DOX loaded PLGA microspheres(DOX-MS)were fabricated via a double emulsion-solvent evaporation method.The sizes,encapsulation efficiency and initial burst release of the DOX-MS prepared were characterized,and the preparation conditions were optimized.The effect on release profiles of DOX from the DOX-MMS with IOs coated layers was investigated.The magnetic responsive release behavior and the mechanisms of drug release of DOX-MMS were observed under ACMF.The thermal-chemotherapy of DOX-MMS was verified in 4T1 breast cancer cell and tumor xenografts.2.The preparation of magnetic induced gas-generating PLGA microspheres and their application in thermal-chemotherapy.The intelligent drug platform,based on the gas-generating mechanism with response to environment stimulation,has a significant advantage in cancer therapy.On the basis of previous studies,we developed magnetic induced as-generating PLGA microspheres(DOX-GMMS),the gas agent(ammonium bicarbonate,ABC),was encapsulated in the core of PLGA microsphere.Firstly,the ABC and DOX loaded PLGA microspheres(ABC-MS)were fabricated via a double emulsion-solvent evaporation method.The structure,sizes and encapsulation efficiency of the ABC-MS prepared was characterized.The formation of CO2 bubbles was examined using an ultrasound imaging system.The magnetic responsive release behavior and the mechanisms of DOX-GMMS were observed.Through the combination of external magnetic field stimulation,interlocking thermal effect of internal ABC response,gas cavitation effect and drug release treatment effect,a new type of magnetic thermal-chemotherapy and other ways to achieve high efficiency in the treatment of cancer.