NIR Dye-functionalized Magnetic Nanoparticles Probe For Cancer Theranostics

Cancer seriously threats people’s health and life.The key to improve the recovery rate and the patients quality of life is tumor of early diagnosis and accurate diagnosis.Thus,the major objective of modern medicine is to develop of high-end,accurate and top diagnostic technique.With rapid progress of imaging,especially molecular imaging,is playing an increasingly important role in early diagnosis of disease,activity of drug screening,and even real-time evaluation of therapeutic effects.In recent years,The nano probe as a molecular imaging contrast agents has developed vigorously because of its advantage of penetrability,high resolution,biocompatibility and function diversity and so on.In this thesis,We developed two new molecular imaging contrast agents,which applied to multimodal imaging and optical treatment.The research content includes:1.Tumor targeting cyanine dye conjugated iron oxide nanoparticles for NIRF/MR dual modal in vivo.Firstly,We are screening to a cyanine dye molecules of tumor targeting.And then,made the targeting Cy5 molecules conjugated to the iron oxide nanoparticles surface by chemical modification form a novel kind of nano probe that is Cy5-Fe₃O₄ for tumor targeting and NIRF/MR dual modal in vivo.Cells in vitro experimental results show that Cy5molecules transmembrane transport into the cell and located to the mitochondria by cell membrane of organic anion transporting polypeptides（OATPs）mediated.The cell membrane of organic anion transporting polypeptides（OATPs）overexpressed of tumor cell,so cyanine dye（Cy5）have targeted tumor cells.Double modal in vivo imaging experiments show that Cy5 functionalized iron oxide nano probe displayed good tumor targeting ability,which capable to NIRF/MR dual modal imaging in vivo.This research provides a new way of thinkingfor designing of new molecular imaging nano probe and tumor targeting imaging.2.Tumor targeting of IR808-MnO nano probe for multimodal imaging in vivo.The second work designed a magnetic nano probe that a NIR small molecules of ramification IR808 functionalized MnO nanoparticles and apllied to tumor targeting multimodal imaging in vivo.This formation of nano probe is that IR808 dye assembled into what amphiphilic polymer coverted of magnetic nanoparticles MnO surface by covalent crosslinking.The cell experimental results show that IR808-Mn O nano probe targeted tumor cell by IR808 mediated,and located in mitochondria.The living imaging experimental results show that the IR808-Mn O nano probe would targeted tumor,also performed specific NIRF/PA/MR imaging as an efficient and stable targeting multimodal imaging nano probe.It have better tumor targeting effect compared with free IR808,and solved metabolism,unstable of the small molecular free IR808 of disadvantages.This study providing a potentially attractive tumor diagnosis method for clinical application.3.Cancer targeted photodynamic/photothermal therapy on the basis of tumor targeting of IR808-MnO nano probe for multimodal imaging in vivo.This study make use of that on the basis of the second work developed of IR808-Mn O nano probe which have effect on specific response and producting oxygen against in allusion to tumor microenvironment of H⁺/H₂O₂,and applied to cancer targeted photodynamic/photothermal therapy.In vitro experimental results show that under the irradiation of 808 nm laser IR808-MnO nano photosensitizer producted reactive oxygen species（ROS）,and also could produce higher local temperature.Simulated the tumor microenvironment in vitro of cell therapy the results show that IR808-MnO nano photosensitizer showed good effect of PDT/PTT in vitro cell therapy.The results show that IR808-Mn O nano photosensitizer had very good optical treatment effect in vivo experiment.This study conclusion suggests that IR808-Mn O photosensitizer has efficient specificity tumor targeting,relieving cancer slightly acidic environment,improving the tumor hypoxia environment,generating ROS as killing tumor cells,which improved the effect of the PDT/PTT treatment.Thus,it resolved to the problem of lack of targeting,light toxicity,insufficient treatment effect of the traditional photosensitizer.On the basis of the second study,the research work not only to achieve the high efficiency,high selectivity of tumor photodynamic/photothermal therapy,and implements the curative effect of monitoring.