| Organic conjugated materials have high applicability in the fields of biosensing,imaging,and therapy due to their excellent optoelectronic properties and low biotoxicity.Phototherapy is an emerging light-triggered cancer treatment method,which has attracted much attention due to its advantages of non-invasiveness,high spatiotemporal selectivity,and low side effects.Phototherapy mainly includes photodynamic therapy(PDT)and photothermal therapy(PTT).PDT converts the surrounding molecular oxygen into cytotoxic reactive oxygen species through photosensitizer electron or energy transfer,so as to kill tumor cells.PTT ablates tumor cells by converting nearinfrared light into heat by photothermal agents.Fluorescence imaging is a new non-invasive imaging method,which has the the advantages of high sensitivity,quick responsehigh stability,low hazard and low cost.It can be combined with various cancer treatment method to achieve precise diagnosis and therapy of tumours.The research shows that there is still an urgent need to obtain materials that absorb and emit in the near-infrared band,improve their water solubility and biocompatibility,and combine the advantages of other materials to prepare composite nanomaterials through the structural design and structure-activity relationship research of organic conjugated materials.It can further enhance its application effect in the fields of near-infrared fluorescence imaging,photothermal/photodynamic synergistic therapy,and targeted diagnosis and treatment.Diketopyrrolopyrrole(DPP)has high planarity and electron deficiency,and can be used as electron acceptor(A)to conjugate with various electron donors(D)to construct derivatives with D-A-D structure,which is expected to achieve good nearinfrared absorption,photothermal properties,photoacoustic properties and certain photodynamic properties.In response to the above problems,this paper carried out direct arylation polymerization(DHAP)of DPP derivatives with fluorene derivatives,thiophene and other monomers,and introduced polyethylene glycol(PEG)side chains into the monomers to improve water solubility.A series of water-soluble conjugated polymers were synthesized and the structure-activity relationships were studied.In addition,composite nanomaterials were constructed based on water-soluble DPP small molecule derivative for biosensing and targeted diagnosis and treatment.The main research contents are as follows:1.Different ratios of PEG-grafted DPP derivatives,PEG-grafted fluorene derivatives and dithiophene were polymerized to synthesize P1,P2 and P3 by DHAP method.With the increase of fluorene derivatives and the decrease of dithiophene,the absorption intensity of the polymer in the near-infrared region decreased,and the water solubility increased accordingly.The singlet oxygen yields of P1,P2 and P3 were 23.7%,20.1% and 25.8%,respectively,with little difference between them,and the photothermal conversion efficiency gradually increased,which were 34.0%,44.2% and52.0%,respectively.The experiments on He La tumor cells confirmed that P1 and P3 have good photothermal/photodynamic synergistic therapeutic effect when excited at 635 nm,and that they can effectively inhibit the growth of tumor cells,and have good biocompatibility.2.The absorption or emission of most organic conjugated materials are mainly in the first nearinfrared region(NIR-I,650～1000 nm),while studies have shown that the penetration depth of light in the second near-infrared region(NIR-II,1000～1700 nm)is much larger than that of NIR-I light,so it has a greater advantage in the diagnosis and treatment of deep tumors.PEG-grafted DPP derivatives,PEG-grafted fluorene derivatives and DPP derivatives with long alkyl side chains were polymerized by DHAP method.P4 has a broad NIR absorption range(500～1300 nm),and two fluorescence emission peaks can be seen at 1150 nm and 1300 nm when excited by an 808 nm laser.The singlet oxygen yield of P4 was 21.5%,and the photothermal conversion efficiencies under excitation at 808 nm and 1064 nm were 45.0% and 52.2%,respectively.This means that P4 can be excited by NIR-II fluorescence for phototherapy.The He La tumor cell experiments confirmed that P4 has a good photothermal/photodynamic synergistic therapeutic effect when excited at 1064 nm,and that it can effectively inhibit the growth of tumor cells,and has good biocompatibility.3.HA-AuNPs were obtained by modifying gold nanoparticles(Au NPs)with negatively charged tumor-targeting biomolecule hyaluronic acid(HA),which self-assembled with positively charged water-soluble FDF into composite nanomaterials.Since Au NPs can quench the fluorescence of FDF through the fluorescence resonance energy transfer(FRET)effect,and the high concentration of hyaluronidase(HAase)in tumor cells will gradually degrade the HA-Au NPs/FDF,the quenched fluorescence of FDF will recover.Therefore,HA-Au NPs/FDF can rapidly and quantitatively detect HAase by the degree of fluorescence recovery,with a detection limit of 0.04 U/m L.Moreover,the singlet oxygen yield of HA-Au NPs/FDF was 23.7%,and the photothermal conversion efficiency was21.3%.The He La cell experiments confirmed that HA-Au NPs/FDF could effectively inhibit the growth of HeLa cells. |
