Design And Study Of Fullerene-doxorubicin Derivatives

The carbon cage structure of fullerenes has produced its unique physicochemical properties,showing excellent application prospects in anti-tumor,antioxidation,scavenging free radicals,drug carriers and so on.But fullerene is not conducive to application in biological systems due to the solubility of fullerene in water.The most common solutions are to chemically modify the carbon cage that hydrophilic branches are introduced.And they also rely on the EPR effect of nanoparticles to prepare them for conversion into aqueous suspension nanotechnology for use in biological systems.As a broad-spectrum chemotherapeutic drug,adriamycin has a strong side effect on normal cytotoxicity and poor targeting ability of tumor cells.Based on fullerene derivatives excellent biological activity,this paper designed the fullerene derivatives and anti-cancer drug doxorubicin three ways of molecular connections in order to reduce the dosage and side effects of doxorubicin,strengthen its therapeutic effect.In this paper,we first studied the combination of fullerenes derivatives and doxorubicin non-covalent bonding,and the composition of the complex was quantitatively analyzed by ultraviolet analysis.Then we studied the combination of fullerenes derivatives and doxorubicin,and synthesized fullerene amino acid doxorubicin(FD(DOX),FE(DOX))and fullerene aspartate Hydrazone bond doxorubicin(FD=DOX).In this way,the nanometer water suspensions of fullerene-doxorubicin derivatives was prepared,their scavenging effects on superoxide anion and hydroxyl radical and the bacteriostatic activity of fullerene aspartate doxorubicin were studied.The results are as follows:1.Ultraviolet spectrophotometer was used to measure the different concentration of doxorubicin hydrochloride solution under a specific wavelength of 480 nm absorbance value,making its in 5% DMSO concentration and absorbance of standard curve y = 0.02683 + 0.00892 x.When the ratio of FPy to doxorubicin hydrochloride was 1: 2.5,the composite effect was the best.2.Fullerene amino acid was successfully synthesized,and the product structure was confirmed by UV-vis,IR,MALDI-TOF,and the product was well dissolved in DMSO.3.Synthesis of fullerene-aspartic acid hydrazone doxorubicin,and the product was characterized by UV-vis and IR.4.15 mmoL/L nano-water suspension of fullerenin-doxorubicin derivatives were prepared by organic solvent mediated method.The distribution range of n-FD(DOX)by the particle size meter is 50.2 to 215.8 nm,and D(90%)is 89.8 nm.The distribution range of n-(FPy-DOX)by the particle size meter is 89.8 to 578.6 nm,and D(90%)is 112.9 nm,which were the ideal size of nanometer particle size.5.Determination results of the biological activity of fullerene-doxorubicin derivatives: 1)Determination of superoxide Anion scavenging ability of Fullerene-doxorubicin derivatives nano-water suspension by pyrogallol system,Under dark conditions,they can scavenge superoxide anion,of which n-FD(DOX)is the best.2)Methyl violet Fenton system was used to determine their ability to scavenge hydroxyl radical,both of them could scavenge hydroxyl radicals under dark conditions,and the scavenging capacity of n-FD(DOX)was higher than that of other fullerenin-doxorubicin derivatives and mannitol at the same concentration.However,However,the ability of n-FD=DOX to produce free radicals under illumination is higher than that of n-FD(DOX)and n-(FPy-DOX)at the same concentration.3)n-FD(DOX)had no inhibitory effect on e.coli of gram-negative bacteria,and had obvious inhibitory effect on the gram-positive staphylococcus aureus.The results show that the fullerene derivative synthesized by different methods still has the function of scavenging free radicals,which is expected to further explore the effect of the compound on the tumor cells of the living body.