Study On The Preparation And Synergistic Antitumor Effects Of Magnetic Targeting Muli-function Drug Carriers

At present,cancer is one of the malignant diseases which still threaten the health of human beings.The traditional method like chemotherapy for treating cancer presents non-specific distribution in the body and easy to bring a series of side effects.Hence,reducing these side effects effectively and improving the therapeutic effects have always been difficult problems for researchers to solve.On the one hand,the construction of multifunctional nanoplateforms,including magnetic targeting,controlled acid-sensitive drug release and so on,plays an important role in reducing the side effects of chemotherapy and improving the effect of targeted chemotherapy on cancer cells,and becomes one of the hot research directions.On the other hand,emerging phototherapy,such as photothermal therapy(PTT)and photodynamic therapy(PDT),has the advantages of high accuracy,good controllability and small side effects.Therefore,therapeutic combined chemotherapy with PTT or PDT plays abetter effect in synergistic anti-tumor.And exploring suitable photothermal agent and photosensitizer become the key point of the researches in this field.However,the anoxic microenvironment of tumor cells seriously restricts the effect of photosensitizer during PDT process.Thus,solving the problem of low oxygen content in tumor cells has become one of the goals we need to work on.Taking these problems into consideration,our work in this paper is carried on as follows:1.The Fe3O4 nanoparticle synthesized via a solvo-thermal method as a core and the ZIF-8 shell was in-situ synthesized through oil bath with the addition of Zn(NO3)2·6(H2O)and 2-methyl imidazole at first.Afterwards,the sample was carbonized under Ar and air atmosphere subsequently in the tube furnace and Fe3O4@C/ZnO nanomaterials with porous core-shell structure were obtained.Then the ligand targeting agent of folate(FA)was introduced with the amidation reaction and the obtained product was marked as Fe3O4@C/ZnO-FA.According to the results of magnetic performance testing,the magnetic saturation intensity of Fe3O4@C/ZnO reaches 39.07 eum/g,which indicates the outstanding magnetic targeting ability.And the results of the temperature over light curve showed the good photothermal conversion effect of Fe3O4@C/ZnO nanomaterial,where the temperature increases around 17 ? after irradiated with 638 nm laser for 17 min.Meanwhile,the drug DOX could be loaded into Fe3O4@C/ZnO-FA and the encapsulation efficiency reach up to 64.35 ?g/mg due to the porous structure.Moreover,the pH sensitive ZnO in Fe3O4@C/ZnO-FA-DOX composites owns a "gatekeeper" function due to ZnO could dissolve in the condition of weak acidity of tumor cells.Therefore,we have investigated the in vitro release of DOX from Fe3O4@C/ZnQ-DOX under different pH(7.4,6.5,and 5.0)conditions.And the results showed that the the release of chemotherapeutic drug DOX in Fe3O4@C/ZnO-FA-DOX composite is pH sensitive,which imply that Fe3O4@C/ZnO-DOX nanomaterials can achieve controlled drug release.Finally,the cell MTT and fluorescence microscopy showed that the synergistic effect of the chemotherapy and photothermal therapy of composited drug carrier can effectively kill tumor cells,and the cell uptake experiments showed that the composite have great potential application in the biomedical field.2.Similarly,we first synthesized Fe3O4 as the core and introduced MnO2 shell through the in-situ reduction of KMnO4 in concentrated hydrochloric acid solution.The Fe3O4@MnO2 nano-materials with mesoporous petal structure was obtained.Then the ternary composite of Fe3O4@MnO2@PPy was obtained by in-situ oxidation polymerization,which was initiated by the Fe3+ produced by Fe3O4 in acid environment,of pyrrole monomer.The hysteresis regression curve shows that the magnetic saturation intensity of this composite is 28 emu/g,which indicate that the composite has a certain degree of magnetic targeting performance.The composite Fe3O4@MnO2@PPy not only has photothermal transformation and photodynamic effect through the tests of light heating and single-wire oxygen generation but also could catalyze the production of sufficient O2,which could alleviate the degree of anoxia of tumor cells to improve the effect of photodynamic,well from H2O2 under the condition of weak acidity.Notably,the loading rate of the composite to the chemotherapeutic drug DOX was 70%.Through cell MTT experiment,fluorescence microscope image and cell phagocytosis test,it shows that the composite has superior effect on endocytosis of cells.So that it can assist the subsequent synergistic treatment effect of chemotherapy,PTT and PDT,which helps kill tumor cells more effectively.3.The lamellar structured g-C3N4 was obtained by the calcination of melamine,and then Fe3O4 nanoparticles were attached to the surface of g-C3N4 by coprecipitation effect with the addition of FeC;3·6H2O and FeCl2·4H2O.Finally,the Fe3O4/g-C3N4@PPy composite was.obtained by in-situ oxidation polymerization of pyrrole monomer.The magnetic saturation intensity of the composite measured by hysteresis regression curve reaches 34 emu/g,which indicating that the composite,owns magnetic targeting ability.The dispersion of the composite was irradiated with laser at 638 nm for 10 min,and the temperature increased by at least 18 ?.Moreover,DPBF was used as the indicator of singlet oxygen and the results showed that the composite has good photothermal conversion and photodynamic effect.At the same time,we also detected that the composite could catalyze the photolysis of H2O to produce O2 under the irradiation of 638 nm laser.It is possible that the heterojunction existing in Fe3O4/g-C3N4@PPy could reduce the band gap and increase the photocatalytic activity of generating O2.Additionally,MTT assay,fluorescence microscope imaging and cell phagocytosis test indicated that the excellent endocytosis of the composite and outstanding synergistic antitumor effect of chemotherapy,PTT and PDT.