Application Of Commercial Rhenium Sulfide In Gastrointestinal Tract Spectral CT Imaging And Photothermal Therapy Of Tumors

Part 1 Facile Synthesis of Rhenium Sulfide Gum as a Biosafe Spectral1111 CT Contrast Agent for Gastsrointestinal Tract Imaging in VivoObjective:The clinically iodinated contrast agents show poor signal-to-noise ratio,and emerging heavy-metal-based CT contrast agents usually suffer from tedious synthetic methods and harsh reaction conditions,and undefined biosafety concern.In view of this situation,we study made full use of the physiochemical features of commercial rhenium sulfide（ReS₂）powder,and developed a high-efficient and low-toxic spectral CT contrast agent with facile and green synthesis.Subjects and Methods:The rhenium sulfide gum（XG-ReS₂）was simply synthesized by adding solid commercial ReS₂ powder into the xanthan gum（XG）solution.The spectral Hounsfield unit curves of XG-ReS₂ and iohexol were determined,and their spectral CT imaging was compared in vivo.Furthermore,in vivo the biosafety of XG-ReS₂was assessed by body weight monitoring and histopathological analysis of various important organs.Result:The XG-ReS₂ prepared by simple mixing and stirring at room temperature exhibited favorable colloidal stability,high-performance CT,and spectral CT contrast capacity.In vitro CT imaging data showed that XG-ReS₂ has strong X-ray attenuation capability even at high electron energy,confirming its feasibility as a contrast agent for spectral CT imaging.The proposed XG-ReS₂ not only guarantees obvious contrast enhancement in gastrointestinal tract via spectral CT imaging,but also demonstrates the low toxicity in vivo.Conclusion:XG-ReS₂,as a contrast agent for spectral CT imaging,has the advantages of simple synthesis process,high signal-to-noise ratio and good biological safety.The strong and constant X-ray absorption ability of XG-ReS₂ at any energy ensures its superior enhanced spectral CT imaging,and enables effective distinction in the region of interest and surrounding tissues with an ultrahigh signal-to-noise ratio.Compared with iohexol,the XG-ReS₂ with fascinating features gives detailed visualizing for the gastrointestinal tract through CT and spectral CT imaging.More importantly,the only mixing procedure is so simple that the ready-to-use XG-ReS₂ can be produced in large-scale in a short time,which is very suitable for potential clinic application frequently.We believe that the―ready-to-use‖preparation mode provides a novel way for the development of new contrast agents.Part 2 Turning Commercial Rhenium Sulfide Powder into Hydrogel for Enhanced NIR-II Photothermal TherapyObjective: So far,only a few nanomaterials have been reported for the second near-infrared（NIR-II）window photothermal therapy（PTT）,which still face inevitable limitations such as complicated preparation steps,difficulty in large-scale production and potential biological toxicity.In order to obtain NIR-II photothermal agents with mass production and better biocompatiblity,we use a simple and green strategy of ―turning solid into gel‖ to make water-insoluble commercial rhenium sulfide（ReS₂）powder into hydrogel for enhanced NIR-II PTT.Subjects and Methods: The Alginate-Ca²⁺-rhenium-sulfide(ALG-Ca²⁺-ReS₂)hydrogel was simply synthesized by adding solid commercial ReS₂ powder into the alginate-Ca²⁺(ALG-Ca²⁺)hydrogel according to our previous report with some modification.Briefly,ALG-Ca²⁺ hydrogel was synthesized by mixing calcium chloride solution with sodium alginate solution,and then the commercial ReS₂ powder was added,followed by vigorous stirring to generate homogeneous ALG-Ca²⁺-ReS₂ hydrogel.We used scanning electron microscope,UV-3600 plus spectrophotometer,and IR thermal camera to characterize the morphology,near-infrared absorption spectrum,and photothermal conversion properties of ALG-Ca²⁺-ReS₂ hydrogel.Cytotoxicity and photothermal ablation ability of ALG-Ca²⁺-ReS₂ hydrogel in vitro were determined by standard MTT assay.The photothermal property of ALG-Ca²⁺-ReS₂ hydrogel was assessed by photothermal tumor ablation in vivo.The in vivo biosafety of ALG-Ca²⁺-ReS₂ hydrogel was assessed by body weight monitoring and histopathological analysis of various important organs.Result: The ALG-Ca²⁺-ReS₂ hydrogel prepared by simple mixing and stirring at room temperature exhibited favorable colloidal stability,good syringeability and excellent NIR-II photothermal conversion capability.The cellular experiments demonstrated the low cytotoxicity of ALG-Ca²⁺-ReS₂ hydrogel and high efficient NIR-II PTT in vitro,and in vivo toxicity assessments further confirmed the good biocompatibility of ALG-Ca²⁺-ReS₂ hydrogel.Moreover,in vivo tumor treatment experiment demonstrated the ALG-Ca²⁺-ReS₂ hydrogel can be used for high-efficient NIR-II PTT of tumors by simple non-invasive injection.Conclusion: In summary,we use a simple strategy of ―turning solid into gel‖ to make water-insoluble commercial ReS₂ powder into hydrogel.The experimental results showed that ALG-Ca²⁺-ReS₂ hydrogel has excellent NIR-II photothermal conversion ability and good PTT effect both in vitro and in vivo.In addition,ALG-Ca²⁺-ReS₂ hydrogel with good biosafety and large-scale production capacity showed great clinical application prospects.More importantly,the developed ALG-Ca²⁺-ReS₂ hydrogel not only makes commercial ReS₂ powder bioavailable,but also opens a new way to develop novel therapeutic agents for clinic applications without safety concerns.