Research On Anti-tumor Activity Of Functionalized MoSe₂ Nanomaterial And Its Multimodal Imaging

Cancer has become one of the most serious diseases to human health.Obviously,the new requirement of current tumor diagnosis and treatment is early diagnosis,accurate detection and effective treatment.At present,clinically used tumor imaging techniques include ultrasound imaging（US）,fluorescent imaging,magnetic resonance imaging（MRI）,X ray computed tomography（CT）,and photoacoustic imaging（PA）,et al.However,there are some limitations to the individual imaging methods,and the tumor diagnosis is generally based on the morphologic changes of the tumor,therefore,it will be difficult for early tumor discovery and prompt treatment.Besides,the existing cancer treatment methods,such as surgery,chemotherapy and radiotherapy,are not ideal.Therefore,we must to innovate the means of diagnosis and treatment,explore new and effective strategies for cancer diagnosis and treatment,improve the accuracy of early tumor diagnosis and enhance the effect of treatment.Hence,with the rapid development of medical imaging and nanotechnology,scholars put forward two new concepts-----multimodal imaging and theranostics.In order to make up for the shortcomings of individual imaging,a variety of imaging methods are integrated to improve the accuracy of imaging,which will be an inevitable trend in the development of medical imaging and be also of great potential value in clinical application.The general diagnosis and treatment of cancer are two independent processes,and there are many unstable factors in this long process,which can lead to a poor therapeutic effect of cancer treatment.If the diagnosis and treatment process of cancer can be combined organically,we will achieve a new integrated medical mode.The tumor related information can be accurately acquired by using various imaging functions of theranostics reagents.On this basis,individualized treatment plan is developed for early diagnosis and effective treatment of cancer,which will have the opportunity to become the mainstream of cancer research.Based on this,the multifunctional contrast agent and cancer treatment drugs are loaded on the same nanocarrier for multimodal imaging to diagnose disease and monitor the treatment process,which will provide new ideas and strategies for the treatment of cancer.Based on the above research background,a series of theranostics nanodrugs for diagnosis and treatment of cancer were designed and synthesized in this paper.The purpose of this paper is to find a new theranostics nanosystem with imaging and cancer treatment simultaneously,to reduce the toxicity of traditional medicine and improve its antitumor activity,and give it the imaging function to the nano system and diagnose diseases monitor the treatment process.The full text is divided into three chapters.In chapter 1,it briefly introduces the research progress of two dimensional transitional metal dichalcogenides in biomedicine and the research progress of modern antitumor strategies.It focuses on the new tumor optical therapy and the significance of multimodal imaging and theranostics in the field of cancer diagnosis and treatment.At the same time,the purpose and significance of this research are expounded.In chapter 2,we investigated the Gd³⁺-doped molybdenum selenide nanosheets for bimodal imaging and the effect of cancer photothermal therapy.A simple liquid-phase method was used to prepare Gd³⁺-doped MoSe₂ nanosheets,and then using poly（ethylene glycol）modification on the surface,the theranostic MoSe₂(Gd³⁺)-PEG nanosheets with high stability in physiological solution and low toxicity in vitro were obtained,realizing bimodal imaging to guide cancer photothermal therapy.It revealed that Gd³⁺used as a paramagnetic material for MoSe₂(Gd³⁺)-PEG provided a strong contrast effect in magnetic resonance imaging,furthermore,the MoSe₂ showed strong absorption in the near infrared region,therefore,MoSe₂(Gd³⁺)-PEG could be used as contrast agent for photoacoustic imaging（PAI）and photothermal agent for photothermal therapy.In vitro cell experiments,due to the better photothermal property of MoSe₂(Gd³⁺)-PEG nanosheets,it could effectively ablate tumor cells.In vivo experiments,after intravenous injection of MoSe₂(Gd³⁺)-PEG to those mice with subcutaneous tumor,an enhanced permeability and retention effect was found at the tumor by magnetic resonance/photoacoustic bimodal imaging.In vivo antitumor experiments proved that MoSe₂(Gd³⁺)-PEG nanosheets have significant antitumor effect.In chapter 3,we first studied the MoSe₂ nanoflowers loaded indocyanine green to achieve significant cancer combination therapy.Combined with the second chapter that is the in-depth study of inorganic material MoSe₂,the MoSe₂ nanoflower carrier was innovatively synthesized,and then loaded indocyanine green as a photosensitizer.Finally,responsive polydopamine and tumor-targeted hyaluronic acid were modified on its surface to construct a theranostic nanossystem（MoSe₂@ICG-PDA-HA）for photothermal/photodynamic therapy in cancer.In vitro cytotoxicity test showed that MoSe₂@ICG-PDA-HA has a better biocompatibility.In vitro apoptosis experiments proved that MoSe₂@ICG-PDA-HA could induce apoptosis of tumor cells significantly under laser irradiation.3D multicellular spheroids experiments indicated that MoSe₂@ICG-PDA-HA has good penetration depth（⁸0 m）and significant cell ablation effect.Finally,in vivo experiments showed that MoSe₂@ICG-PDA-HA not only has significant anticancer effect,but also good anti-migration and anti-proliferative effects.