Nano Molybdenum Disulfide For Multimode Imaging And Phototherapy Of Tumors

Clinical treatments for cancer such as surgical therapy,chemotherapy,and radiation therapy often have certain shortcomings and limitations.Hence,it highly needs to find new type of cancer treatment with low invasion.Phototherapy is one of recently developed technologies for the cancer therapy on the merits of easy operation,non-invasion,localized ablation,and triggering antitumor immunity.Few-layer MoS₂ nanosheet is a very promising photoactive probe in virtue of strong absorbance in near-infrared region and easily functionalized surface.Herein,we designed a theranostic nanoplatform with MoS₂ nanosheets for realizing the desired imaging-guided phototherapy.Firstly,the synthesis of MoS₂ nanosheets was carried out by hydrothermal method,and then BSA decoration of MoS₂ has been made to improve its biocompatibility.After that,morphological feature,crystalline phase,optical absorption properties of the sample were observed by transmission electron microscopy,X-ray diffraction analysis,and ultraviolet-visible-near infrared absorption spectrum,respectively.The results revealed that BSA decorated MoS₂ with reasonable dimension,high photothermal conversion efficiency and good stability.Therefore,it was suitable for later phototherapy.In this thesis,the results showed the MoS₂ nanosheets not only can convert light energy into heat energy efficiently,but also generate singlet oxygen and has the function of photoacoustic imaging.Therefore,this thesis realized photoacoustic imaging-guided photothermal/photodynamic combined cancer treatment just via a single material of MoS₂ nanosheets.Both of in vitro MTT and in vivo phototherapeutic investigation showed that BSA-MoS₂ had a favorable biocompatibility.Detection of mitochondria membrane potential indicated that the MoS₂ can induce the cell death through a mitochondria-dependent pathway.In a further study,BSA-Mo S₂ nanosheets were used to eliminate solid tumors of the HepG2-tumor bearing mice.During the treatment,the photoacoustic imaging and conjugation with Cy5.5 for fluorescence imaging were used for depicting tumors.In addition,B-mode ultrasonography?US?was employed to monitor the evolution process of solid tumor.The result suggested that the tumor underwent a liquefaction necrosis process.Histology analysis verified the good biocompatibility of BSA-MoS₂ and the metabolic pathway of BSA-MoS₂ is through the liver and spleen to a largely extent.The BSA-MoS₂ alone lacks of active-targeting properties.This thesis further introduced function of targeting to enhance the precision of treatment.It was reported that macrophages can endocytose nanomaterials.Furthermore,it can recognize the cytokines secreted by tumor cells and migrate to tumor spheroids.Nanomaterials delivery system is designed by loading BSA-MoS₂ nanosheets into macrophages to realize tumor targeted phototherapy.The macrophages endocytosed-BSA-MoS₂ presented nearly the same photothermal behavior to that of BSA-MoS₂ under equivalent concentration.As expected,the active targeting phototherapy was realized.Both of B-mode US and histology analysis were used to investigate the treatment outcome and biocompatibility of macrophages endocytosed-BSA-MoS₂ mediated phototherapy process.It has been observed that macrophages endocytosed-BSA-MoS₂ delivered with caudal vein showed the same therapeutic effect to that BSA-MoS₂ delivered through intratumor injection.In addition,there is no detectable lesion on the major organs after the treatment,indicating the good bio-safety of this process.In summary,MoS₂ nanosheets are excellent theranostic agent,which realized the photoacoustic and fluorescence imaging guided phototherapy.After loaded into macrophages,the MoS₂ nanosheets realized tumor targeted phototherapy.