Multi-modality Optical Imaging For Tumor Integrated Diagnosis And Treatment Based On Two-dimensional Silicon Nanosheets

The difficulty in dynamic tracking the tumor angiogenesis changes is major obstacle in the path toward outstanding outcomes for nanotheranostics in tumor treatment.Conventional molecular imaging techniques are often lacking the microscopic assessment the vascular morphometrics of tumor,especially on quantifying microvascular hemodynamics before and after the nanotherapeutics.Micromagnetic resonance imaging(Magnetic resonance imaging,MRI),ultrasound imaging(Ultrasound,US),laser confocal microscopy(Laser confocal microscope,LCM)and other traditional imaging techniques have been applied in the study of vascular development.However,these tools have their own limitations when it comes to angiography.The main limitations of MRI are long time consuming and low resolution.Ultrasound imaging can detect the large vessels of the body in real time,but it is difficult to achieve cellular resolution imaging of tissues.Although LCM can achieve high spatial resolution images,it usually requires an exogenous fluorescent probe and cannot achieve unlabeled angiography.Therefore,it is difficult for the above traditional imaging techniques to carry out unlabeled,high-resolution in vivo imaging to study tumor vascular development and treatment process.The high resolution and high contrast imaging technique is of great significance for understanding the morphological and functional changes of the vascular system during tumor development.When a single imaging mode no longer meets the needs of clinical and basic research,it is necessary to combine the advantages of each imaging with multimodal imaging methods.Herein,we present a triple-modality photoacoustic(Photoacoustic imaging,PA)imaging-optical coherence tomography angiography(Optical coherence tomography angiography,OCTA)-laser speckle imaging(Laser speckle imaging,LSI)strategy,which isnot only able to precisely guide the thermo-chemotherapy of tumor,but also capable oflong-term continuous investigatingthe microvessel morphological and hemodynamics changes during tumor growth and after tumor treatment in vivo.Besides,to precisely implement the tumor thermo-chemotherapy treatment via triple-modality imaging strategy,a two-dimensional(2D)5-fluorouracil silicon nanosheets(5-Fu-Si NSs)therapeutic agent isutilized.Furthermore,the tumor tissue properties including blood oxygen saturation(SaO2),hemoglobin content(HbT),and tumor microvascular parameters including microvascular density(MVD),and relative blood flow(RBF)are quantified during the tumor development and thermo-chemotherapy in vivo.Notably,in vitro and in vivo results jointly demonstrate that 5-Fu-Si NSs have excellent PA imaging efficacy,high photothermal conversion efficacy(45.8%),and more effective cancer treatment.Further,2D high resolution tumor microvascular images in different stage display that tendency of the thermo-chemotherapy effect is closely associated to tumor angiogenesis.Taken together,our investigations establish the fundamental base in theory and technology for further tailoring the novel specific diagnosis and treatment strategy in tumor.More importantly,this feasibility study would be beneficialto evaluate the tumor microvascular response to nanotherapeutics at microscale.It is of great significance for the diagnosis and treatment of systemic microcirculation disorders.