Magnetic Targeting Drug Delivery System Based On Magnetic Porous Carbon Nanospheres

Magnetic targeting drug delivery system has attracted widespread attentions in biological medicine field owing to its high efficiency and low toxicity for cancer therapy.Many researchers devoted themselves to the study of drug carriers with excellent results.But the problems of low drug-loading capacity and fast drug release rate still need to be solved.Magnetic porous carbon nanospheres(MPCNs)possess the features of both magnetic nanoparticles and porous carbon nanomaterials,such as magnetism,low density,good chemical stability,thermal stability,low toxicity,rich porous structure and high specific surface area.The surface of MPCNs also possesses abundant oxygen-containing functional groups,drug molecule can be directly loaded in the pores or on the surface of MPCNs.The drug-loading capacity of MPCNs could be improved.In addition,environment-responsive materials can be grafted on the surface of MPCNs to control the drug release.Therefore,MPCNs as drug carrier will hopefully solve the problems of low drug-loading capacity and fast drug release rate.Under such background,this paper focuses on the preparation,characteration and application of MPCNs including magnetic microporous carbon nanospheres(MM-PCNs),magnetic ordered mesoporous carbonnanospheres(MOM-PCNs)and thermosensitive MOM-PCNs(TMOM-PCNs).The detailed conclusions are as follows:1.The preparation of MM-PCNs and their drug-loading performance.First,Na2SO4 and FeCl3 were chosen as raw materials to prepare α-Fe2O3nanoparticles(α-FNPs).The influences of reaction time and the concentration of FeCl3 on α-FNPs were discussed.The results show that the α-FNPs meet the requirements of drug carrier when the reaction time is 9 h,the concentration of FeCl3 is 0.01 mol/L and the reaction temperature is 180℃.The morphology ofα-FNPs is spherical and regular,the average particle size is ~68 nm.Second,α-FNPs,glucose and ZnCl2 were chosen as iron source,carbon source and chemical activation agent,respectively,to prepare MM-PCNs by hydrothermal method combining with annealing treatment.The quantity of ZnCl2 was screened and the results revealed that the specific surface area(SBET)of MM-PCNs is first increased and then decreased.The highest SBET is 480.32 m2/g,the average pore size is 1.169 nm,the pore volume is 0.239 cm3/g,and the intensity of saturated magnetization(Ms)is 30.6 emu/g.At last,the feasibility of MM-PCNs as drug carrier was investigated by choosing methylene blue(MB)as template drug molecule.The drug-loading capacity of MM-PCNs for MB is56.44 mg/g,which is lower than that reported in literatures.Therefore,the drug-loading capacity of MM-PCNs should be further increased.2.The preparation of MOM-PCNs and their performance of controlled drug release.In order to improve the drug-loading capacity and the ability of controlled drug release of drug carrier.First,phenol and formaldehyde were chosen as raw materials,α-FNPs as catalyst and F127 as soft template agent to synthesize ordered mesoporous carbon nanospheres(OM-PCNs)by hydrothermal soft template method combining with annealing treatment.The influences of the concentration of α-FNPs and reaction time on morphology of OM-PCNs were discussed.The results indicated that the morphology of OM-PCNs is excellent and the average particle size is ~106 nm when theconcentration of α-FNPs is 0.78 mmol/L and the reaction time is 16 h.Second,MOM-PCNs were synthesized by using Fe(NO3)3·9H2O as iron source by impregnation method.The results indicate that the SBET of MOM-PCNs reaches344.906 m2/g,the pore size is 3.037 nm and pore volume is 0.4063 cm3/g,Ms is11.93 emu/g.MOM-PCNs possess the peculiarity of magnetic hyperthermia and the normalized specific absorption rate(SAR)is 37.24 W/g in alternating magnetic field.Third,the performances of drug loading and drug release were investigated,revealing that the drug-loading capacity of MOM-PCNs for doxorubicin hydrochloride(DOX)reaches 284.7 mg/g,the drug release rate can be controlled by adjusting p H value,the drug release rate reaches 23% and release time is 20 h.3.The preparation of TMOM-PCNs and their performance of controlled drug release.In order to further improve the ability of controlled drug release of drug carrier,MOM-PCNs and N-isopropyl acrylamide(NIPAM)were used as substrate and functional monomer,respectively,to synthesize TMOM-PCNs by silanization modification and radical polymerization method.The quantity of NIPAM was screened,indicating that the morphology of TMOM-PCNs is satisfactory when the mass ratio of silanie-modified MOM-PCNs to NIPAM is 1:3.The lower critical solution temperature is 39.5℃,Ms is 10.31 emu/g.Normalized SAR reaches 30.23 W/g in alternating magnetic field,which indicate that TMOM-PCNs possess the peculiarity of magnetic hyperthermia.At last,The performance of controlled drug release of TMOM-PCNs was studied,the results indicate that the drug-loading capacity of MOM-PCNs for DOX reaches 141.2 mg/g.The DOX release rate can be controlled by adjusting pH value and temperature.The drug release rate is65.29% and release time is 20 h when pH decreases to 5.5.The DOX release rate increases from 30% to 37% and release time is 20 h when the temperature increases from 37 to 45℃.