Nano-theranostics Based On Fused-Ring-Electron-Deficient Cores:Synthesis,Properties And Bioapplications

Malignant tumors are a serious threat to the health of people.If the tumor is found at an advanced stage,most patients have no chance of radical surgery.Therefore,early diagnosis and treatment of cancer is crucial.Fluorescence probes and optical imaging techniques have attracted great attention for their ability to study biological processes at the cellular level.Compared with other clinical imaging techniques,fluorescence angiography is very useful for studying the molecular level due to its good spatial resolution,high sensitivity at the single-molecule level,better signal-to-noise ratio,superior specificity for biochemical activity and non-destructiveness.The biological processes on the surface provide great benefits and are very helpful for early disease diagnosis.Photodynamic therapy is an excellent tumor treatment method due to its precise controllability,minimal invasiveness,high spatiotemporal precision,and has been used in clinical treatment.At present,the fluorescent materials used for tumor therapy and diagnosis probes are roughly divided into two categories:Nano inorganic fluorescent material materials and organic molecular fluorescent materials.Inorganic nanoparticles are slowly excreted after administration,but mainly remain in most organs of the reticuloendothelial system,such as the liver and spleen,thus causing long-term toxicity.In contrast,benign and biologically inert components of organic optical agents composed entirely of organic materials can provide bio-optical advantages while avoiding toxicity problems.However,the poor solubility of most organic dyes can lead to severe self-aggregation in aqueous environments,making cellular uptake more difficult,and most organic materials are prone to fluorescence quenching in the aggregated state.In order to overcome these difficulties,in this paper,two systems are constructed by using fused-ring electron acceptors with long-wave emission,aggregation state,good photochemical stability,strong molecular designability,and convenient energy level regulation,namely the PDI system and the J-aggregation system,four novel PDI derivative molecules and J-aggregation molecule TPAAP were prepared,and it was proved from the cellular level that they have the functions of excellent fluorescence imaging diagnosis and photodynamic therapy at the same time.Its content is divided into the following two aspects:1.Bioimaging and photodynamic therapy based on perylene diimide（PDI）derivatives.We chose mono-and di-bromo-substituted PDI to couple the polycyclic aromatic hydrocarbon 9-phenanthrene to obtain four new molecules PDI-ph,PDI-ph-R,PDI-diph,PDI-diph-R.The molecular structure was confirmed by hydrogen spectrum,carbon spectrum,mass spectrometry,and the CV test calculation results were basically consistent with the molecular simulation HUMO and LOMO energy levels,and through the characterization of spectrum,and photodynamics,we found that PDI-ph has excellent photostability and has highest singlet oxygen yield.Therefore,we choose PDI-ph molecules for biological applications.We encapsulated PDI-ph with the amphiphilic polymer F127,and performed MTT cytotoxicity experiments and intracellular confocal imaging on the prepared nanoparticles.Fluorescence imaging can be achieved in cells,and tumor cells can be killed by light.2.Bioimaging and photodynamic applications based on J-Aggregation nanoprobe.We prepared TPAAP by the most classical chemical synthesis method,and confirmed the molecular structure by hydrogen spectrum,carbon spectrum,mass spectrometry,etc.The CV test calculation results are basically consistent with the molecular simulation HOMO and LUMO energy levels,and the S₁ and T₁ test results are consistent with the theoretical calculation values.We use the J-aggregation properties of molecules to control the fluorescence properties of the prepared nanoparticles in liquid phase,and the prepared near-infrared fluorescent nanoparticles meet the expectations with a singlet oxygen yield of 40%and a maximum emission wavelength of 700 nm.The results of biological experiments also confirmed that TPAAP NPs can perform intracellular fluorescence imaging.Due to the Voleculear J-aggregation characteristics,the intracellular fluorescence imaging effect is good,and the higher the content of TPAAP NPs,the better the killing effect of Hela cells.