Multi-Modal Theranostic Nanoprobes Based On Second Near-Infrared Emission Silver Sulfide Quantum Dots

With the continuous development of nanotechnology in recent years,nanomaterials have developed rapidly in the fields of biology,chemistry,and medicine,especially in the diagnosis and treatment of tumors.They have unique advantages.Researchers apply the interaction relationship between photons and nanomaterials to the exploration of life sciences.This is a huge advancement in the history of human science.Using effective control synthesis steps and methods,nano-biomaterials are prepared to realize a variety of different active or passive photonics functions.When the appropriate frequency of light radiation is on the tumor site enriched with a large number of nanomaterials,the nanomaterials will absorb energy and transition to different electronic excited states,and produce various phenomenon of light,sound,heat,etc.in the form of radiation transitions or non-radiation transitions.And then they can be applied to various diagnosis and treatment of tumor tissues.With the development of cross-integration of life science and optical technology,optical imaging,as an important biological imaging method,including imaging technologies such as fluorescence imaging and photoacoustic imaging,has attracted widespread attention from scientific researchers.In recent years,fluorescence imaging technology has been widely used in the field of biomedical imaging,and is also used clinically to distinguish normal tissues from diseased tissues to guide tumor surgery.Compared with traditional imaging techniques such as tomography,fluorescence-based optical imaging has the characteristics of fast feedback and high spatial resolution.Since biological tissues are in the near-infrared second zone(NIR-II,1000-1700 nm)region,the autofluorescence of tissues and the absorption and scattering of photons are small,so NIR-II fluorescent dyes have a higher signal-to-noise ratio and larger tissue penetration depth,so the development of fluorescent reagents based on the near-infrared two-zone is particularly important.Photothermal therapy(PTT),gas therapy(GT)and chemodynamic therapy(CDT),as new and efficient tumor therapies,have the characteristics of good curative effect,strong controllability,and small side effects,which have attracted widespread attention of scientific researchers.However,as far as a single therapy is concerned,there are certain limitations,that is,it will cause incomplete tumor treatment.In response to some problems in the current research,this thesis designed and developed two diagnostic and therapeutic probes based on silver sulfide quantum dots(Ag₂S QDs).The main research contents are as follows:1.A multifunctional nanoprobe based on Ag₂S@SiO₂-DHA/SNP/TD-FA NPs was constructed.The Ag₂S in the nanoprobe has good NIR-II fluorescence imaging and photoacoustic imaging performance,and can be used for NIR-II fluorescence and photoacoustic imaging diagnosis of tumor cells.At the same time,the nanoprobe produces a photothermal effect under near-infrared illumination conditions,which makes the phase change material 1-Tetradecanol(1-Tetradecanol,1-TD)melt and release the loaded drug molecules.The thermally released sodium nitroprusside(SNP)can continuously consume the over-expressed glutathione(GSH)in the tumor at the tumor site,and produce NO to provide gas therapy;on the other hand,the ferrous ions produced by it can further interact with the released dihydrogen ions.Artemisinin reacts to produce reactive oxygen species(ROS),which in turn enhances the therapeutic effect of dihydroartemisinin(DHA).In short,the nanoprobe can be used for PTT/GT/CT combined therapy guided by NIR-II fluorescence/photoacoustic dual-modal imaging.In vivo experiments show that the multifunctional nanoprobe can achieve combined therapy for tumors.A better treatment effect.2.Using the coordination of metal ion Fe³⁺and carboxyl modified silver sulfide quantum dots(Ag₂S QDs)and thiadiazolobenzotriazole nanodots(TBZ dots),Ag₂S-Fe-TBZ self-assembled nanoparticles were synthesized.Due to the presence of Fe³⁺,the nanoparticle itself has no NIR-II fluorescence,but exhibits a good fluorescence recovery effect in the presence of GSH and H₂O₂,thereby realizing activated NIR-II fluorescence imaging in response to the tumor microenvironment.The nanoparticles are degraded in the tumor microenvironment where GSH and H₂O₂ are overexpressed to produce Fe³⁺/Fe²⁺.While the fluorescence is restored,it also produces Fe²⁺,which can be used for chemical motility.Mechanical treatment,and the introduction of Fe³⁺ions as a contrast agent for magnetic resonance imaging.The nano-material(Ag₂S-Fe-TBZ)has the multi-functional nano-diagnosis and treatment performance of PTT/CDT combined therapy guided by the three-modality imaging of NIR-II fluorescence(FL),photoacoustic(PA)and magnetic resonance(MRI).The tumor microenvironment-responsive near-infrared light-triggered multi-mode diagnosis and treatment nano platform developed in this paper has broad application prospects in clinical tumor diagnosis and treatment.