Metal-Containing Functional Polymers Based On Energy Transfer:Design,Synthesis And Biological Applications

Metal-containing functional polymers are emerging as a class of interesting and widely used materials in biomedical fields,because they have rich molecular structures,easy chemical modification,convenient integration of functional units and good biocompatibility.From main group metals to transition metals and lanthanides,a diverse range of metal centers can be chosen to tune the polymer properties.Moreover,the linkages that bind to the metal centers can vary from covalent bonds to electrostatic interactions and coordination bonds,which endow the polymers with various response performance to microenvironmental factors.People can utilize this strategy for designing different kinds of polymers,which will meet the requirements in biological areas.So far,owning to the excellent photophysical properties,phosphorescent transition metal complexes are considered as a new class of photofunctional materials for biomedical imaging,biological detection and cancer photodynamic therapy.Based on the above consideration and rich choice of polymers,the transition metal complexes and other functional luminophores can be combined through covalent bonds.By regulating the energy transfer process between iridium（Ⅲ）complexes and other components reasonably,dual-emissive and long-lived polymer platforms can be developed.By using ratiometric and time-resolved luminescence imaging technique,the sensitivity of detection and signal-to-noise ratio of imaging can be improved significantly.In addition,by introducing different environmental sensitive functional groups into the polymer,novel polymer platforms for biomedical applications can be established.The major contents of this thesis are listed below:1.The design and synthesis of dual-emissive and water-soluble phosphorescent conjugated polymers for heparin detection and celluar imagingA series of conjugated polymers for heparin detection have been designed and synthesized.The polymers contain polyfluorene as the main chains,hexylic quaternary ammonium salt as side chains and different iridium（Ⅲ）complexes as the phosphorescent luminophors.Due to the quaternized side chain,the polymers can self-assemble in water to form nanoparticles with the size of 50 nm so that they can well disperse in water.The polyfluorene backbone and the iridium（Ⅲ）complexes constitute an effective fluorescence resonance energy transfer（FRET）pair,which realize the ratiometric detection for heparin successfully.We have studied the changes in morphology and energy transfer process of polymers after adding negatively charged heparin into the polymer solution in detail.And heparin detection performance has been optimized by screening a series of conjugated polymers.In addition,the polymers exhibit good cell membrane targeting performance,which has been utilized for time-resolved luminescence imaging of cancer cells.All the results show that the conjugated polymers can significantly improve signal-to-noise ratio of sensing and imaging.2.The design and synthesis of responsive polymers containing Ir（Ⅲ）and Eu（Ⅲ）complexes for pH and temperature sensingA series of poly-2-（dibutylamino）ethyl methacrylate or poly-N-isopropylacrylamide containing iridium（Ⅲ）complexes and europium（Ⅲ）chelates have been designed and synthesized.The non-conjugated polymers are chosen to act as the backbone,which greatly increases the biocompatibility of the polymers.Meanwhile,this kind of polymers can tune their configuration more easily than the conjugated ones with rigid backbone when microenvironment changes.In addition,a novel kind of iridium（Ⅲ）complexes consisting of 4-（2’-pyridyl）benzoic acid as main ligands and bipyridine derivative as auxiliary ligands have been introduced into the polymers.Because the triplet-state energy level of iridium（Ⅲ）complexes matches well with the excited-state energy level of europium（Ⅲ）ions,the europium centre can be successfully sensitized under the excitation of 520 nm,which largely extends the application in biological areas.Furthermore,depending on the pH response of 2-（dibutylamino）ethyl methacrylate and temperature response of N-isopropylacrylamide,the sensing of pH and temperature has been realized in cancer cells successfully.By utilizing the ratiometric and time-resolved luminescence imaging technique,the sensitivity of detection and signal-to-noise ratio of imaging are greatly improved.3.The design and synthesis of dual-emissive near-infrared phosphorescent conjugated polymers for cancer theranostic via ratiometric and phosphorescence lifetime imagingA new kind of dual-emissive semiconducting polymer nanoparticle（SPN）containing fluorescent BODIPY derivatives and near-infrared（NIR）phosphorescent iridium（Ⅲ）complexes has been designed and synthesized.Triethylene glycol was chosen as the side chain of the polymer.After further quaternization,the polymers can form nanoparticles with the size of 20 nm,which improves their dispersity in aqueous solution.Meanwhile,the conjugated backbone of SPNs provides effective shielding for the two luminophors from photobleaching.In the SPNs,the BODIPY units serve as the energy donors in FRET process for enhancing the light absorption of the SPNs.The NIR emissive iridium（Ⅲ）complexes are chosen as the energy acceptors and efficient photosensitizers.The synergistic effect of BODIPY units and iridium（Ⅲ）complexes through FRET process contributes to the overall excellent performance of the SPNs-based PSs.And the high ¹O₂ yield（0.97）of the SPNs is among the best value of PSs.In addition,on account of the phosphorescence quenching of iridium（Ⅲ）complexes caused by oxygen,the SPNs can also be utilized for oxygen mapping in vitro and in vivo,which assist in the evaluation of PDT process and provide important instructions in early-stage cancer diagnosis.