Unimolecular Micellization For The Emission Of Star Conjugated Polymers And Its Applications

Conjugated polymers are the long π-delocalized polymers with carbon-carbon single bond,double bond or triple bond backbone. Conjugated polymers have become a promising fieldin interdisciplinary subject of chemistry and material science, due to their uniqueflorescence/phosphorescence or conductive properties. Among various conjugated polymers,the hyperbranched conjugated polymers have highly branched three-dimensional architecture.Compared with those of linear conjugated polymers, hyperbranched conjugated polymersshow good optical properties under the aggregated state. To construct the unimolecularmicelle system, other functional polymers, such as amphiphility, stimuli-responsibility andso on, have been introduced onto the surface of hyperbranched conjugated polymers toextend the application of conjugate polymers and develop newly functional materials. In thisdissertation, based on the summarization of previous research works about the influence ofself-assembly on the optical properties of conjugated polymers, poly（ethylene glycol） andpoly（2-（dimethylamino） ethyl methacrylate） chain were introduced into hyperbranchedconjugated polymer to form the star conjugated copolymer. With the helpf of unimolecularmicellization strategy, the conjugated nanoparticles with different functionalization wereprepared through self-assembly, temperature variation and organic/inorganic hybridapproaches, which could be used in various applications, like nano-science and bioimaing.The main research contents and results are shown as follows:1. Self-assembly control of the optical properties of star conjugated copolymerSelf-assembly approach to tune the optical properties of the star conjugated copolymer hasbeen developed. The hyperbranched conjugated polymer （HCP） was synthesized via Wittigcoupling reaction of N-（n-hexyl）-3,6-diformylcarbazole and1,3,5-bis[（p-triphenyl phosphonio） methyl] benzene tribromide. Subsequently, the linear poly（ethylene glycol）arms were grafted onto the HCP by acylhydrazone connection to form the star conjugatedcopolymer （HCP-star-PEG）. The structures of HCP and HCP-star-PEG were characterizedby NMR, FTIR and GPC techniques. Due to its amphiphilic structure, HCP-star-PEG couldself-assemble in the co-solvent of chloroform and acetonitrile. The morphologies and opticalproperties of HCP-star-PEG had been characterized by DLS, TEM, NMR and UV-visspectra. Owing to the protonation of imine group （C=N） in acyldydrazone bond in the acidcondition, the conjugation of HCP-star-PEG increased and the optical properties changedfrom pale green to red. Co-solvent self-assembly would affect the protonation of imine groupgreatly, resulting in the control of optical properties of HCP-star-PEG.2. Emission enhancement of conjugated polymer through self-assembly ofunimolecular micelles to multi-micelle aggregatesThe emission of star conjugated copolymer （HCP-star-PEG） was enhanced greatly byco-solvent self-assembly approach. Owing to the three-dimensional architecture ofhyperbranched conjugated polymer, the HCP-star-PEG could form multi-micelle aggregatesfrom unimolecular micelles, which was characterized by DLS and TEM. For themulti-micelle aggregates, the HCP core was well wrapped in the interior of the unimolecularmicelles by PEG arms, resulting in emission enhancement of HCP-star-PEG in the aggregatestate through restriction of concentration self-quenching and intermolecular aggregation ofconjugated polymer core. The length of PEG arm showed great influence on the size andoptical properties of self-assembled HCP-star-PEG. The high emission of HCP-star-PEGmicelles exhibits excellent cellular imaging application.3. Real-time monitoring of drug release from star conjugated copolymer in tumor cellStar conjugated copolymer was used as drug carrier to monitor the drug release in tumorcell by fluorescent change. The star conjugated copolymer combined hyperbranchedconjugated polymer core and poly（ethylene glycol） arms with acylhydrazone or ether linkagewas synthesized successfully, named as HCP-star-PEG and HCP-O-PEG, respectively. Thestructures of HCP-star-PEG and HCP-O-PEG were characterized by NMR, FTIR, GPC,TGA, etc. The DLS and TEM results confirmed that star conjugated polymers self-assemblyinto multi-micelle aggregates from unimolecular micelles. The in vitro cytotoxicity ofHCP-star-PEG and HCP-O-PEG micelles was evaluated by MTT assay against NIH-3T3normal cells. The cell viabilities after48h incubation with star conjugated copolymers at concentration of1mg/mL remained above80%, compared to the untreated cells. The resultssuggested that HCP-star-PEG and HCP-O-PEG showed the low cytotoxicity. Doxorubicin（DOX）, used as model drug, was encapsulated into star conjugated copolymer micelles. Invitro release studies demonstrated that the release of DOX from micelles was significantlyfaster at mildly acid pH of5.0compared to physiological pH of7.4. Owing to the existenceof acylhydrazone bond, the release of drug from HCP-star-PEG micelles was much fasterthan that from HCP-O-PEG micelles at acid environment. The emission of star conjugatedcopolymer was quenched efficiently by DOX through π-π stacking and fluorescenceresonance energy transfer. After DOX release from polymeric micelles, the fluorescentintensity of HCP-star-PEG or HCP-O-PEG was recovered gradually. The fluorescencechange of star conjugated copolymer demonstrates the drug release in tumor cell.4. Temperature-induced emission enhancement of star conjugated copolymer withthermo-responsive poly（2-（dimethylamino） ethyl methacrylate） coronas for bacteriadetectionA facile strategy for temperature-induced emission enhancement of star copolymer hasbeen developed. The star polymers （HCP-star-PDMAEMA） with different PDMAEMAchain length were synthesized successfully from the hyperbranched conjugated polymermacroinitiator by atom transfer radical polymerization （ATRP）. The structures ofHCP-star-PDMAEMAs were characterized by NMR, FTIR, GPC and TGA. Thevariable-temperature UV-vis measurements confirmed that star conjugated copolymersexhibited classical thermo-responsive phase transitions with adjustable lower critical solutiontemperature （LCST）, depending on the pH of copolymer solution. Above the LCST, theemission of HCP-star-PDMAEMA was enhanced greatly through restriction ofintermolecular aggregation of conjugated polymer core. The emission performance ofHCP-star-PDMAEMA could be readily adjusted by changing PDMAEMA length. Thistemperature-dependent emission enhancement of HCP-star-PDMAEMA is a good candidatefor detection of E. coil.5. Highly fluorescent core-shell hybrid nanoparticles from unimolecular starconjugated polymer for biological toolHighly fluorescent unimolecular core-shell hybrid nanoparticles （HCP@SiO₂） wereprepared for their application in biological imaging. The nanoparticles were readilyfabricated from the soft template of unimolecular star conjugated polymer （HCP-star-PDMAEMA） under mild condition, which were confirmed by FTIR, TGA, DLSand EDS. With the isolation of hyperbranched conjugated polymer （HCP） core from SiO₂shell, the fluorescent performance of HCP@SiO₂were retained in the aqueous solution. Thecytotoxicity of HCP@SiO₂was evaluated by MTT assay against NIH-3T3normal cells.After24h incubation with HCP@SiO₂at concentration of500μg/mL, the cell viabilitiesremained above90%compared with the untreated cells, suggesting the low cytotoxicity ofHCP@SiO₂. This highly fluorescent HCP@SiO₂could be used as biological imaging. Theflow cytometry and fluorescence microscope measurements demonstrated that the surfacecharge of HCP@SiO₂had profound effect on the cellular uptake of nanoparticles by HeLacells.