Design And Construction Of Two-dimensional Layered Nanomaterials And Their Application In Tumor Diagnosis And Treatment

As a disease with extremely high fatality rate,cancer has always been a serious threat to human health.Traditional cancer treatment methods inevitably attack normal cells while killing cancer cells and cause many side effects,which prompts people to develop more precise and effective treatment strategies.In recent years,photothermal therapy(PTT),chemodynamic therapy(CDT)and gas therapy have the characteristics of small side effects and non-invasiveness,which have attracted wide attention of researchers.The mechanism of these treatment methods is mainly to use the characteristics of the therapeutic agent to generate thermal or strong oxidative ROS in response to external stimuli or tumor microenvironment,thereby causing cell death.The current commonly used therapeutic reagents have certain deficiencies,such as poor water solubility and biocompatibility,low light absorption performance in the nearinfrared region and low drug loading,which severely limit their therapeutic efficiency.Recently,the rapid development of nanomaterials has provided new opportunities for overcoming the shortcomings of traditional diagnostic and therapeutic reagents.Among them,the two-dimensional layered nanomaterials can be combined with various drug molecules due to their large specific surface area and high drug loading to achieve synergistic treatment of multiple therapies and obtain highly effective therapeutic effects.Inspired by this,this article carefully designed and constructed a variety of two-dimensional layered nanomaterials for cancer treatment.The specific research is as follows:(1)Design and construct a B4C@C two-dimensional layered nanomaterial with high efficiency of light-to-heat conversion in the near-infrared second biological window(NIR-?).The nanomaterial is prepared by calcining B4C and glucose by the traditional hydrothermal method.It has strong light absorption under the near-infrared second window(NIR-?:1000-1350 nm).Compared with the raw material B4C reagent,the molar extinction coefficient and photothermal conversion efficiency of B4C@C have been significantly improved.In vitro and in vivo experiments also show that the material has good biocompatibility.Under 1064 nm laser irradiation,the B4C@C nanomaterial exhibits excellent tumor suppressive effect.In living animal models,it can be seen that B4C@C can effectively ablate tumor tissue.In addition,the nanomaterial can also be used for NIR-? photoacoustic imaging,which shows a good tumor diagnosis and treatment effect and has broad application prospects.(2)A new type of two-dimensional layered ZnMnAl-LDH/Arg nanoreagent was constructed for the synergistic treatment of tumor cells with chemodynamic therapy(CDT)and nitric oxide(NO)gas therapy.The ZnMnAlLDH nano-reagent with uniform size and large specific surface area was prepared by co-precipitation method,and then loaded with the NO donor Larginine(Arg)to synthesize a new type of ZnMnAl-LDH/Arg two dimensional layered nanomaterials.The material can rapidly degrade and release Mn2+ in a weakly acidic tumor environment.Mn2+ has a Fenton-like effect and can catalyze the decomposition of excess H2O2 in the tumor microenvironment to generate reactive oxygen species(ROS)to achieve effective CDT.In addition,high concentrations of H2O2 can react with Arg to generate NO.NO gas(concentration range of 1 ?M-1 mM)can cause cancer cell DNA deamination and inhibit the repair of damaged DNA.The experimental results show that ZnMnAl-LDH/Arg can effectively generate ROS and control the release of NO in the tumor microenvironment induced by H2O2.It has a synergistic therapeutic effect of CDT and NO gas therapy,and shows great prospects in cancer treatment.(3)Construct a two-dimensional layered MgAl-LDH/Hemin nanomaterial that responds to tumor microenvironmental stimuli.MgAl-LDH nano-reagents with uniform size were prepared by co-precipitation method,and Hemin was loaded on MgAl-LDH by electrostatic adsorption.Due to the protective effect of MgAl-LDH,Hemin effectively solves the shortcomings of poor water solubility,easy agglomeration and instability,and improves the efficiency of Hemin to generate singlet oxygen under light,effectively improving the effect of photodynamic therapy(PDT).