The Design,Syntheses And Photoacoustic Imaging Applications Of Conjugated Polymers In Second Near-Infrared Window

Objective:A non-planar donor strategy was used to synthesize D-π-A and D-A conjugated polymers with absorption in the second near-infrared window,providing a new strategy for the design and synthesis of high-performance polymer-based photoacoustic imaging contrast agents.Methods:（1）Monomer and polymer synthesis:The monomers and polymers were synthesized by chemical means,and the structures of monomers and polymers were determined by ¹H NMR,¹³C NMR,mass spectrometry,thermogravimetric analysis and infrared spectrum;In this paper,three strategies were adopted to design and synthesise polymeric materials,including non-planarity modulation of conjugated polymer donor units,D-A alternation to narrow the band gap and extension of side chain length to increase polymer solubility.（2）Preparation of nanoparticles:Water-soluble nanoparticles were prepared by coating amphiphilic block polymers.（3）Performance test of the polymer:The thermal stability of the polymer was evaluated by thermogravimetric analysis.The absorption curve of the polymer was obtained by UV-Vis-NIR absorption spectroscopy of the polymer and the polymer film to determine the spectral absorption range of the polymer.The electrochemical properties of the polymer were determined by cyclic voltammetry（CV）.（4）Performance test of nanoparticles:In order to evaluate the stability of nanoparticles,the morphology and size of nanoparticles were evaluated by transmission electron microscopy.The surface potential of the nanoparticles and the stability of the 14-day particle size of the nanoparticles were tested by a nanoparticle size analyzer.（5）Biocompatibility and imaging performance test:the biocompatibility of the nanoparticles prepared by the polymer was evaluated by cytotoxicity experiments and H&E staining experiments.The imaging performance of the nanoparticles was evaluated in vitro and in vivo.Results:（1）in Chapter 2,NIR-II D-π-A type conjugated polymers,named PTT-DTBBT and PTT-DTPSe,with alkoxy-substituted bithiophene（TT）as the non-planar electron donor,and benzothiadiazole（BBT）and pyridineselenadiazole（PSe）as the electron acceptors,respectively,were synthesized.Thermogravimetric analysis showed that the polymers possessed good thermal stability,with temperatures of 294°C and 252°C respectively at 5%polymer weight loss.The absorption spectra of the polymers showed that PTT-DTBBT exhibited stronger absorption peaks in the range of 1000-1800 nm and had a redshifted absorption spectrum comparing to that of PTT-DTPSe.PTT-DTBBT and PTT-DTPSe had narrow band gaps of 0.63 e V and 1.11 e V,respectively,which were consistent with the results derived from density function theory（DFT）.The averaged hydrodynamic radii of PTT-DTBBT@NPs and PTT-DTPSe@NPs were152.2 nm and 161.2 nm,respectively,and the particle size was found to have little change within two weeks,indicating that both the PTT-DTBBT@NPs and PTT-DTPSe@NPs have good stability performance and are not prone to aggregation and cleavage.The biocompatibility of the nanoparticles was evaluated by cytotoxicity assay and H&E-stained sections of vital organs,the results showed that both the polymer nanoparticles have good biocompatibility and tissue safety.The solid model was used to simulate in vitro conditions,and it was found that the injection concentration was positively correlated with the signal intensity.In vivo vascular imaging showed that NIR-II minimized tissue scattering and autofluorescence.（2）In Chapter 3,the D-A material PTT-ATQ,which uses alkoxy-substituted bithiophene（TT）as a non-planar electron donor and strongly electron withdrawing unit thiadiazole quinoxaline（ATQ）as electron acceptors,was synthesized.When the polymer loses weight by 5%,the temperature is 287°C,reflecting the excellent thermal stability of the polymer.The PTT-ATQ band gap was measured electrochemically at0.62 e V with a narrower band gap.The nanoparticles were regularly spherical,the average hydrodynamic radius was measured to be about 150 nm,and the nanoparticle size changed little within two weeks,suggesting good stability.Nanomaterials have good biocompatibility,the cytotoxicity results showed that the cell activity was above90%in the concentration range of 0-80μg m L^-1,and no significant cytotoxicity was observed;the results of in vitro haemolysis experiments showed that no significant haemolysis was observed at all concentrations of PTT-ATQ@NPs,indicating that the material has good haemocompatibility;When compared with normal tissues,no obvious effusion damage or necrotic damage was observed,and there were no obvious clinical toxicity symptoms.PTT-ATQ@NPs were observed to have stronger brightness in the in vivo photoacoustic（PA）images obtained under 1064 nm excitation light and with excellent optical properties,which opens up possibilities for in vivo imaging applications.（3）In Chapter 4,on the basis of P-CDT10V-BTZ polymer synthesis,the length of the polymer side chain is extended by the"click chemistry"strategy,and the polymer P-CDT10V-SO-BTZ with NIR-II absorption is synthesized.The synthesis of target products was verified by nuclear magnetic resonance and infrared spectroscopy.To verify the increased solubility of the polymer,we carried out theoretical calculations and experimental tests,and found that the solubility was significantly better after“click”.The polymer was encapsulated by DSPE-PEG2000 to obtain P-CDT10V-SO-BTZ@NPs,and the performance of the nanoparticles was analyzed and evaluated by the optical performance test,stability test and biocompatibility test.The polymer material has a wide absorption band from 570 nm to 1370 nm.The surface potential of PTT-ATQ@NPs is-38.8m V,and the high surface negative potential indicates that the nanoparticles are not easy to aggregate.At the administration concentration of 95μg·m L^-1,the cell survival rate was above 90%,which indicated that P-CDT10V-SO-BTZ@NPs nanomaterials had low cytotoxicity and good biological safety.Conclusion:1.In this paper,D-π-A and D-A conjugated polymers with NIR-II absorption were designed using ether chain substituted bithiophene units as strong donors,demonstrating good biocompatibility,photostability and good photoacoustic imaging signals in mouse dermatomes,and providing a new molecular design strategy for developing conjugated polymers with absorption in the near-infrared II window.2.In this paper,we introduced alkene bonds at the end of dithiophene-cyclopentadiene side chains by click chemistry,and the solubilising groups introduced were able to increase the solubility of the polymer in tetrahydrofuran,providing a new way of thinking about the poor solubility of the polymer during the processing and preparation of nanoparticles.