The Development Of Multifunctional Targeted-nanoparticles' Construction And Its Theranostics

Background Cancer is the leading cause of death in China and is a major public health problem.However,these currently available and useful diagnostic tools are limitated in detecting tumour in their earliest stage of formation.So the theranostics of the multifunctional targeted-nanoparticles attracted considerable attention.Objective In order to develop the multimodal imaging and theranostics of the cancer,we synthesized and characterized the multifunctional namoparticles which own the properties of imaging in vitro and in vivo and evaluated the therapeutic effect of the nanoparticles.Methods 1)Synthesized the RGD-Au DSNS and RGD-Au DSNS/si RNA,and the properties were characterized.The X-ray attenuation property and photothermal property was measured by the CT imaging system and thermocouple thermometer.The in vitro cytotoxicity and cellular uptake is investigated via CCK8 assay and confocal microscopy.2)To explore the therapeutic effect useing the RGD-Au DSNS/si RNA polyplexes for combined PTT and gene therapy of cancer cells in vitro,we used CCK-8 assay and Western Blot to evaluate the viability of U87 MG cells.Then we assayed the H&E-staining of tumor slices and the change of tumor volume to investigate the effcacy of enhanced PTT and gene therapy of tumors.3)The properties of synthesized Cy5.5-Gd-Au DENPs-FA were characterized.The imaging property was measured by the CT imaging system,3.0T MR imaging system and a near-infrared(NIR)optical imaging system.In this study,we confirmed the cellular uptake of nano-probes and investigated its cytotoxicity,biocompacibility,and biodistribution.Results 1)The RGD-Au DSNS and RGD-Au DSNS/si RNA was Synthesized.The RGD-Au DSNSs have a mean diameter of 55.1 ± 12.6 nm and exhibit an apparent surface plasmon resonance(SPR)peak at around 800 nm.The outcome of CT scans and the temperature change demonstrated that the nanoparticles have a good X-ray attenuation property and photothermal conversion efficiency.These nanoparticles are pretty cytocompatible when the Au concentration below 1 m M.2)The CCK8 assay and western blot analysis demonstrated that RGD-Au DSNS/si RNA was utilized for photothermal ablation and gene silencing in vitro.The result of H&E-stained tumor slices and the change of tumor volume suggested that RGD-Au DSNS/si RNA own the better therapeutic effect than the single photothermal ablation and gene silencing in vivo.3)The Cy5.5-Gd-Au DENPs-FA was synthesized and characterized.The characteristic absorption peaks at 280 nm and 650 nm can be assigned to the conjugated FA and Cy5.5 moieties.The average Au core of Cy5.5-Gd-Au DENPs-FA is about 4.0±1.3 nm and the hydrodynamic size is about to be 126.0 nm.The Cy5.5-Gd-Au DENPs-FA can be used for CT/MR/Optical tri-mode imaging,and the effective enhanced CT/MR/optical images were caused by the uptake of the nanoprobes in the tumor cells.Conclusions In summary,we extensively explored the synthesis and the imaging property and evaluated the theranostics effect of the multifunctional nanoprobes.We enhance the diognostic accuracy and realize the theranostics of the cancer in their earliest stage of formation.The findings from this thesis play a crucial role in the early diagnosis and efficient treatment of cancer.