Multi-component Transition Metal-based Nanomaterials For Effective Treatment Of Cancer

Natural environmental pollution and unhealthy living habits have led to an increasing incidence of cancer each year.In early diagnosis,cancer has the highest mortality rate among all diseases due to its rapid spread,easy metastasis,low sensitivity and poor specificity.At present,the traditional therapeutic methods(such as surgery,chemotherapy and radiotherapy)in clinical have disadvantages such as severe trauma,drug resistance and high recurrence rate,which affect the therapeutic effect of cancer.This reality has been driving researchers to develop new and more effective treatments.With the rapid development of safe nanomedicine and nanobiology,it is possible to break through the barriers of cancer treatment by using some functional nanomaterials and corresponding therapeutic technologies.Due to their good plasticity,controllable shape and size,adjustable thermal,magnetic and optical properties,nanomaterials have many unique advantages in cancer diagnosis and treatment.First,taking advantage of the defective vascular system of tumor tissue,the size of nanoparticles gives them enhanced permeability and retention(EPR)effects in tumors.Secondly,the inherent characteristics of nanomaterials,such as magnetic properties and strong NIR absorption properties,make it possible to be considered as diagnostic and therapeutic reagents.In addition,with their high specific surface area and the resulting rich active sites,nanomaterials can be regarded as carriers of anticancer drugs(such as small molecule drugs,RNA and protein),thus enhancing drug uptake by cancer cells and improving drug efficacy.Further surface modification can also give nanomaterials excellent biocompatibility and biological safety.Based on the above characteristics,nanomaterials play an important role in the scientific innovation of cancer diagnosis and treatment.In this paper,a "bottom-up" wet chemical method was used to prepare layered double hydroxides(LDHs)precursors.Then,based on the"topological transformation" property of LDHs nanosheets,ultra-thin chalcogenide nanomaterials were synthesized by in situ selenylation treatment.By adjusting the copper content and further surface modification by NO donor,a diagnostic and treatment system with synergistically enhanced performance was constructed.Furthermore,N-doped Co-Fe bimetallic site nanomaterials were prepared by using metal-organic frameworks(MOFs)as precursors after high temperature carbonization.Since metal is uniformly dispersed at atomic level,they can efficiently catalyze the decomposition of overexpressed H2O2 in TME to produce ·OH,so as to achieve superior anti-tumor therapeutic effect of CDT.The following are the main research and related results:1.Ultra-thin chalcogenide nanomaterials for synergistic photothermal/gas therapy guided by photoacoustic imagingUltra-thin Cu-containing CCFS nanomaterials were prepared by simple topological transformation of CoCuFe-LDH precursor.Furthermore,CCFS-PVP-L-Arg nanocomposite with excellent synergistic anti-tumor therapeutic effect of PTT/GT was constructed by surface functionalization with PVP and L-Arg.Ultra-thin Cu-containing CCFS nanomaterials have strong LSPR absorption properties,and the light absorption in the NIR region is significantly enhanced.As a result,CCFS-PVP-L-Arg nanocomposites exhibit excellent photothermal conversion efficiency.In addition,the acidic microenvironment and overexpressed H2O2 in the tumor tissue trigger NO release in the CCFS-PVP-L-Arg nanocomposites,thus achieving local GT at the tumor site.In vitro experiments showed that the apoptosis rate of HepG2 cells was 91.8%.In vivo experiments showed that CCFS-PVP-L-Arg nanocomposites could effectively inhibit tumor growth with NIR irradiation and achieved complete tumor ablation after treatment2.The study of(Co,Fe)/N-C nanomaterials with bimetallic sites in tumor catalytic therapyZnCo-MoFs were synthesized by a wet chemical method.Then ferric salts were introduced into the ZnCo-MoFs.Furthermore,N-doped Co-Fe bimetallic site((Co,Fe)/N-C)nanomaterials were prepared by high temperature carbonization from ZnCo-MoFs introduced with ferric salts,followed by surface modification with PEG to improve the biocompatibility of(Co,Fe)/N-C nanomaterials.XRD,XPS and Raman spectra excluded the presence of large crystalline particles of Co and Fe-containing species.Zeta potential and dynamic light scattering prove that the obtained(Co,Fe)/N-C nanomaterials have uniform particle size and can exist stably in aqueous solvents.(Co,Fe)/N-C nanomaterials can catalyze H2O2 to produce a large amount of ·OH through the pH-responsive Fenton reaction.Kinetic analysis by TMB showed that(Co,Fe)/N-C-PEG nanometerials had high catalytic performance(Michaelis-Menten constant Km=0.61 mM,maximum velocity Vmax=2.51×10-7 M s-1).In vitro experiments showed that(Co,Fe)/N-C-PEG can be used as a promising catalytic therapeutic agent for the effective treatment of cancer.In conclusion,by in situ topological transformation of the ultrathin CoCuFe-LDH precursor in this work,the successfully prepared ultra-thin chalcogenide NSs can be used as an efficient nanocarrier,which has an excellent future application in precision gas delivery and cancer treatment.Then,using MOFs as precursors,the nanomaterials with N-doped Co-Fe bimetallic sites were prepared by high temperature carbonization.The prepared nanomaterials can be used as a catalytic therapy reagent in response to the imbalance of pH and oxidation reduction state of tumor site to produce ·OH with killing effect on cancer cells,which has an important guiding role in the construction of TME-specific response of nanomedicine.