Exploration Of Transition Metal-based Two-dimensional Nanocomposites In Synergistic Cancer Diagnosis And Therapy

As one of the most lethal diseases,cancer is a constant danger to human health.To face the threat of cancer,synergistic cancer diagnosis and therapy,which combine multiple treatments and imaging modes,have fantastic application prospect.Transition metal-based two-dimensional nanomaterials possess unique surface chemistry,excellent optical properties and easy regulation of elemental composition.Modification of these nanomaterials could further expand their biological applications,which has attracted extensive attention from researchers.However,poor dispersion,insufficient stability and biocompatibility of some transition metal-baesd two-dimensional nanomaterials restrict their in vivo application.Therefore,developing a integrated nanoplatform for multi-modal imaging and synergistic cancer therapy by surface modification(to improve performance in physiological environment),loading various of functional molecules and combining the superior physicochemical property of the nanomaterial itself,owes an expansive prospect in cancer theranostics.This paper focused on the modification of transition metal-based two-dimensional nanomaterials.Through surface coating,the photophysical properties,degradability and response to the tumor microenvironment of the nanomaterial were significantly improved.Moreover,photosensitizer or tumor-targeting molecule was further loaded on the surface of the nanomaterial,which successfully realized efficient multi-modal imaging guided synergistic cancer therapy.Specific research contents are as follows:1.Defective Co(OH)₂nanosheet-based nanocomposite for hypoxia relief and photothermal-enhanced photodynamic therapyPink Co(OH)₂ nanosheet was synthesized by precipitation.After bromine water oxidation and exfoliation by tip-sonication,the size distribution of the nanomaterial decreased to 100?200nm.The color turned to blackish brown and the absorbance at near infrared region was significantly elevated.Subsequently,silica coating was modified on the surface of b-Co(OH)₂to increase its dispersibility and biocompatibility.Eventually,BCS-Ce6 was constructed by covalently linking Ce6 on the surface of silica through amido bond.BCS-Ce6 exhibited excellent photothermal effect under 808 nm laser irradiation,the photothermal conversion efficiency was calculated to be 49.49%.Moreover,the catalase-like activity of BCS-Ce6 could produce oxygen through the decomposition of hydrogen peroxide,which enhanced the generation of ¹O₂ by Ce6.Both in vitro and in vivo experiments showed that BCS-Ce6 could be used for photothermal imaging and fluorescence imaging-guided synergistic photothermal therapy and photodynamic therapy under 660 nm and 808 nm laser irradiation,which presented remarkable anticancer activity.2.Boron-doped theranostic nanoplatform for switchable MRI guided photothermal therapy and chemodynamic therapyUsing MoO₄^2-as the precipitating agent,a multi-component metal oxide with Mn,Fe and Mo element was synthesized through co-precipitation method.The metal oxide was transformed into a boron-doped photothermal agent after the reduction of Na BH₄.Subsequetly,disulfide bond-doped silica was modified on the surface of MFM-B to enhance its stability and dispersibilty in physiological environment.To further improve tumor-targeting ability,hyaluronic acid was then linked on the surface of silica to obtain MFM-B@ss-SiO₂-HA.The results indicated that MFM-B@ss-SiO₂-HA exhibited obvious temperature elevation under808 nm laser illumination,and the photothermal conversion efficiency could reach 71.99%.MFM-B@ss-SiO₂-HA was able to react with excess amount of GSH in tumor microenvironment.MFM-B was exposed when disulfide bond was ruptured by GSH,further releasing Mn²⁺and Fe²⁺for efficient chemodynamic therapy.In the meantime,MFM-B@ss-SiO₂-HA possessed superparamagnetism,which could be used for T₂-weighted MRI.After releasing Mn²⁺and Fe²⁺as paramagnetic metal ions,a conversion of imaging mode from T₂-weighted to T₁-weighted MRI was realized,accompanied by a distinct improvement of signal and contrast.In vivo experiments suggested that MFM-B@ss-SiO₂-HA has excellent biocompatibility,which could completely restrain the proliferation of tumor by synergistic photothermal therapy and chemodynamic therapy.