The Construction Of Amphipathic Fluorescent Conjugated Polymer System And Its Bioapplications

Conjugated polymers exhibit large one/two-photon absorption cross-sections,highfluorescence quantum yields,robust optical performances,and good biocompatibility,so they have been widely applied in molecular detection,biosensor,fluorescence imaging,disease diagnosis and treatment,and many other fields.It was reported that a number of hydrophobic conjugated units in conjugated polymers could provided with molecular wire effect and could amplify fluorescence signal in their dissolved state.However,the emission performances were commonly deteriorated by the inherent?-?interaction from the hydrophobic conjugated units in their agglomerate state at aqueous solution,leading to unusefulness in actual bioapplication.Therefore,how to design and develop novel conjugated systems with excellent water solubility and functions for various bioapplications is still the frontier scientific issue in this field.In this dissertation,based on the strategy of unimolecular micellization for the enhanced emission of amphipathic star conjugated polymers,a series of fluorescent conjugated systems with distinct fluorescent performances have been successfully fabricated by using different strategies?supramolecular noncovalent and stimuli-responsive covalent bonding?.By combining of fluorescence resonance energy transfer?FRET?effect,these conjugated systems not only display specific functions,but also have great potential for a variety of bioapplications including,florescence imaging,drug delivery and controlled release,tumor specific diagnosis,and photodynamic cancer therapy.The main contents and results in this dissertation are shown as follows:1.Supramolecular conjugated nanogels for NIR-excited florescence imagingBased on the host-guest interaction between azobenzene and?-cyclodextrin??-CD?,we developed an amphipathic supramolecular conjugated nanogel for imaging.In this system,a two-photon absorbing,hyperbranched conjugated polymer?HCP?was synthesized by Wittig coupling reaction and modified by?-CD to obtain hydrophobic HCP-CD.Then,by controlling the monomer feed ratios of 6-?3-?3-dimethylaminophenylazo?phenoxy?-hexyl methacrylate?DBAMA?and methacrylate-terminated poly?ethylene glycol??PEGMA?,a series of PDABMA-co-PEGMA copolymers were prepared.Benefitting from the supramolecular self-assembly,the HCP-CD and PDABMA-co-PEGMA could form supramolecular conjugated nanogels.Importantly,upon an identical two-photon NIR excitation,dual-florescence signals?blue and green?were observed due to the FRET effect from HCP to azobenzene.These supramolecular conjugated nanogels offered a good dual-florescence imaging in cancer cells.2.NIR-responsive supramolecular star conjugated polymer for drug controlled releaseBased on the photo-responsive behaviour of azobenzene unit and its host-guest interaction with?-CD,we constructed an amphipathic NIR-responsive supramolecular star conjugated polymer.At first,a two-photon absorbing HCP was synthesized and modified by?-CD to get hydrophobic HCP-CD.Then,dimethylaminoazobenzene?DAB?was grafted on the terminal of PEG,named hydrophilic DAB-PEG.The hydrophobic HCP-CD and hydrophilic DAB-PEG would form an amphiphilic supramolecular star conjugated polymer of HCD-star-PEG by the host-guest interaction and would further self-assemble to get HCD-star-PEG micelles for drug delivery.The DAB groups with lower energy state trans-structure could enter the cavity of?-CD very easily.However,after two-photon NIR-irradiation,the structure of DAB units would change into high energy state cis-structure and emerge from the?-CD cavity,which leaded to the cleavage of DAB-PEG from the HCP-CD and resulted in a disassembly of the HCD-star-PEG micelles.This progress could be used in NIR-triggered drug release.3.Color-convertible conjugated polymer-based H₂O₂ activatable probe for tumor-specific detection and imagingBased on the significant hallmark of up-regulated hydrogen peroxide?H₂O₂?in tumor region,a novel amphipathic conjugated polymer-based H₂O₂ activatable fluorescent probe constructedbyboronatecouplingofahydrophobichyperbranched poly?fluorene-co-2,1,4-benzothiadiazole??HPFBT?core and many hydrophilic poly?ethylene glycol??PEG?arms was built to delineate tumors from normal tissues through an aggregation-enhanced FRET strategy.This color-convertible activatable nano-probes is obviously blue-fluorescent in various normal cells but becomes highly green-emissive in various cancer cells.After intravenous injection to tumor-bearing mice,green fluorescent signals were only detected in tumor tissue.Such a facile and simple methodology without targeting ligands for tumor-specific detection and imaging holds great promises for cancer diagnosis and worthwhile to further development.4.Thermo-responsiveconjugatedphotosensitizationsystemforenhanced photodynamic therapyWe proposed an amphipathic thermo-responsive conjugated photosensitization system for enhanced photodynamic therapy?PDT?.In this system,the fluorescent HCP,with a large two-photon cross sections,acted as a two-photon light-harvesting material to significantly enhance the two-photon properties of the traditional photosensitizer of Chlorin e6?Ce6?through FRET effect.To avoid the aggregation-induced fluorescence quenching by the inherent?-?interaction from the hydrophobic HCP and Ce6 in the aqueous solution,a thermo-responsive hyperbranched polyether?HPE?was set between HCP and Ce6 to enhance the water solubility,named HCP@HPE-Ce6.Under NIR light irradiation,the FRET process from HCP and Ce6 could be readily switched??on??for killing cancer by the collapsed thermo-responsive HPE shell due to the photothermal effect of NIR light.Such NIR-triggered FRET leaded to an enhanced two-photon activity of the traditional pure Ce6,and in turn amplified their cytotoxic singlet oxygen generation.Eventually,both in vitro and in vivo PDT efficiency treated with the thermo-responsive conjugated photosensitization system were dramatically enhanced,as compared to pure Ce6 excited by traditional visible light.