Photoacoustic Imaging And Synergistic Photothermal And Photodynamic Therapy Of Hepatocellular Carcinoma Based On Silicene Composite Nanosheets

Hepatocellular carcinoma（HCC）is one of the malignant tumors with the highest mortality in the world,and the patients with HCC have poor prognosis and high case fatality rate.Fortunately,the continuous development of nanotechnology and nano-biomaterials provides an opportunity for a new mode of diagnosis and treatment of HCC.At present,photothermal therapy（PTT）and photodynamic therapy（PDT）have promise prospective in tumor therapy.Moreover,combining treatment of PTT and PDT can further improve the effect of tumor clearance and have great potential in treatment of HCC.In this study,we construct the Silicene@Mn O_x-MSN-PEG-IR780 composite nanosheets,which is a multi-functional integrated nano-platform of photoacoustic imaging-guided PTT combined with PDT therapy and self-contained oxygen supply through near-infrared（NIR）response,and this multi-functional nano-platform can meet the diverse requirements of diagnosis and treatments of HCC.As a novel two-dimensional nanomaterial,Silicene not only has characteristics of excellent specific surface area,favorable biocompatibility and low toxicity that can be used as a carrier for construction of multi-functional diagnostic agents,but also has outstanding photothermal conversion efficiency that can be used for tumor thermal ablation therapy,thus Silicene has great potential in the biomedicine field.Manganese oxide（Mn O_x）can grow on the surface of Silicene with redox-in situ growth method,and Mn O_xcan react with H₂O₂and H⁺in tumor microenvironment（TME）to produce O₂,which can effectively relieve hypoxia in tumor and improve effect of photodynamic therapy.In addition,mesoporous silica nanoparticles（MSN）is performed to load photosensitizer IR780,which meanwhile has photothermal and photodynamic effect under the excitation of NIR（808 nm）,thus effectively improves the stability of IR780 and prolongs its circulation time in vivo.Modification of nanomaterials with polyethylene glycol（PEG）can improve the stability of nanomaterials and reduce their antigenicity.Besides,Silicene and IR780 can also be used as photoacoustic imaging（PAI）contrast agents to provide potential imaging capabilities for guiding and monitoring the phototherapeutic effect of HCC.In summary,our designed Silicene@Mn O_x-MSN-PEG-IR780 composite nanosheets can realize synergistic photodynamic and photothermal therapy of HCC under the guidance of photoacoustic imaging.The study data suggests that photodynamic therapy alone can only partially inhibit the growth of HCC,while photothermal combined with photodynamic therapy can completely eliminate HCC,and there is no recurrence during the observation period.Subsequently,we further verify the biosafety of Silicene@Mn O_x-MSN-PEG-IR780composite nanosheets,the results show that it has little biological toxicity,but the safety and biocompatibility are favorable,which may promote further clinical transformation of Silicene composite nanosheets.The innovations of this study are as follows:（1）the composite nanosheets based on the new two-dimensional nanomaterial Silicene can be used as photoacoustic imaging contrast agent,which can realize synergistic PTT and PDT for HCC under photoacoustic imaging guidance,and achieve the purpose of integration of diagnosis and treatments;（2）Silicene@Mn O_x-MSN-PEG composite nanosheets modified by PEG can be performed to load photosensitizer IR780,which extremely improves the biocompatibility of IR780 and composite nanosheets;（3）The mode of TME responsive self-sufficient oxygen supply provides a new strategy for achieving the high efficiency of phototherapy;（4）The synthetic methods are uncomplicated and inexpensive,which is beneficial to mass production and has potential clinical application value.