Synthesis And Biological Application Of D-A Type NIR Ⅰ/Ⅱ Conjugated Polymers

Conjugated polymers（CPs）are composed ofπ-conjugated backbone and modifiable side chain.Through the reasonable design of the main chain and side chain structure,the physical and chemical properties of conjugated polymers can be adjusted according to the needs,which makes it widely used in optoelectronic devices,including organic solar cells,organic field effect crystal tubes and organic light-emitting diodes.Compared with small molecular dyes,CPs have higher absorption coefficient,stronger light capture ability,and can amplify sensing signal,which can be used for p H sensing,molecular imaging of tissue and disease biomarkers,photothermal ablation of tumor and photodynamic therapy of cancer.In recent years,a series of CPs emitting from visible light to near infrared（NIR）have been synthesized by changing or modifying the monomer structure of the main chain or side chain,and used in cell imaging and subcellular imaging.In addition,Conjugated polymers nanoparticles（CPNs）are also widely used as photoacoustic contrast agents with high spatial resolution and deep penetration depth.CPNs also show excellent performance in fluorescence and photoacoustic imaging guided photodynamic therapy and photothermal therapy.We designed and synthesized the conjugated polymers with donor-acceptor（D-A）structure and fluorescence emission in NIR Ⅰ/Ⅱ window and studied the performance of CPs in imaging and photodynamic therapy:（1）The same donor unit 2,6-bis（trimethyltin）-4,8-bis（5-（2-ethylhexyl）thiophen-2-yl）benzo[1,2-b:4,5-b’]dithiophene was chosen to copolymerize with cyano-substituted stilbene derivatives and/or（Z）-1,2-bis（4-bromophenyl）-1,2-diphenylethene to yield conjugated polymers with D-A structure and fluorescence emission in NIR Ⅰ/Ⅱ window,and these CPs were formulated into CPNs.Using 9,10-anthracyl-bis（methylene）malonic acid（ABDA）as singlet oxygen trapping agent,P4NPs with the best singlet oxygen generation efficiency was selected by comparing their singlet oxygen generation efficiency.P4 nanoparticles（P4 NPs）have strong photosensitivity,and can generate ¹O₂ under light irradiation and induce significant cell apoptosis.P4 NPs showed significant toxicity to He La cells at the dose of 10μg/m L under white light irradiation with 0.292W/cm²for 10 min.（2）On the basis of binary polymers,a series of ternary conjugated polymers were synthesized by introducing 4,7-dibromobenzo[1,2-c:4,5-c’]bis（[1,2,5]thiadiazole）or 3,6-bis（5-bromothiophe-ne-2-yl）-2,5-bis（2-decyltetr-adecyl）pyrrolo[3,4-c]pyrrole-1,4（2H,5H）-dione as electron acceptors.By comparing the emission spectrum and fluorescence quantum yield,we screened out high-bright NIR-II conjugated polymer nanoparticles,which is expected to be used in deep tissue imaging and diagnosis.The penetration depth of P11 NPs was 0.5 cm.Furthermore,P11 NPs displayed a brighter NIR-II fluorescent signal than that of indocyanine green（ICG）in vivo.