Synthesis And Properties Of Responsive Amphiphilic Block And Hyperbranched Star Copolymers

Recently, stimuli-responsive polymers with different topologies have attracted great attention due to their application in the field of biology. In this dissertation, a series of responsive amphiphilic block and hyperbranched-star copolymers have been synthesized via living radical polymerization and their properties were thoughtfully investigated.First, we prepared a series of responsive block copolymers by living radical polymerization and investigated their properties and applications in drug delivery and cell imaging. We also synthesized a series of responsive hyperbranched star copolymers via reversible addition-fragmentation chain transfer (RAFT) polymerization, and studied their self-assembly behaviors and applications in the biomedical field. The primary results acquired are listed as follows:1.Thermoresponsive double hydrophilic diblock copolymers P(MEO2MA-co-OEGMA)-b-PMAGP with various compositions and molecular weights were prepared by deprotection of amphiphilic diblock copolymers P(MEO2MA-co-OEGMA)-b-PMA1pGP. Dynamic light scattering (DLS)and UV/vis studies showed that the micelles self-assembled from P(MEO2MA-co-OEGMA)-b-PMA1pGP were thermoresponsive.A hydrophobic dye Nile Red could be encapsulated by block copolymers P(MEO2MA-co-OEGMA)-b-PMAGP upon micellization and released upon dissociation of the formed micelles under different temperature.The galactose functional groups in the PMAGP block have specific interaction with HepG2cells.2. Redox-responsive amphiphilic diblock copolymers P(MAGP-co-DMAEMA)-b-PPDSMA were obtained by deprotection of P(MA1pGP-co-DMAEMA)-b-PPDSMA, which were prepared via RAFT polymerization of PDSMA using P(MA1pGP-co-DMAEMA) as macro-RAFT agent. DLS and transmission electron microscopy (TEM) studies showed that diblock copolymers P(MAGP-co-DMAEMA)-b-PPDSMA can self-assemble to form micelles. Doxorubicin (DOX) could be encapsulated by P(MAGP-co-DMAEMA)-b-PPDSMA upon micellization and released upon adding glutathione(GSH) into the micelle solution. The galactose functional groups in the PMAGP block had specific interaction with HepG2cells,and P(MAGP-co-DMAEMA)-b-PPDSMAcan act as gene delivery vehicle. This kind of polymer has potential applications in hepatoma-targeting drug, gene delivery and biodetection.3.Photo-and pH-responsive amphiphilic hyperbranched star copolymers HPMAlpGP(PDMAEMA-co-PSPMA)n were synthesized by RAFT polymerization of DMAEMA and SPMA using hyperbranched PMA1pGP as macro RAFT agent. In aqueous solution, the copolymers self-assembled to form core-shell micelles with HPMA1pGP core and PDMAEMA-co-PSPMA shell. The hydrophobic fluorescent dye nitrobenzoxadiazolyl derivative (NBD) was loaded into the spiropyran-based micelles. The obtained micelles not only have photochromic properties, but also modulate the fluorescence of NBD through fluorescence resonance energy transfer (FRET), which was also observed in living cells. The cytotoxicity of the HPMA1pGP(PDMAEMA-co-PSPMA)n micelles was lower than that of25k PEI All the results revealed that these photoresponsive micelles are good candidate for cell imaging and may find broad applications in biological areas such as biological diagnosis, imaging, and detection.4.Redox-and temperature-responsive amphiphilic hyperbranched star copolymers HPGMAP(MEO2MA-co-OEGMA-co-RhBAMA)ns were synthesized by RAFT polymerization of MEO2MA, OEGMA and RhBAMA using hyperbranched PGMA as macro RAFT agent. UV/vis studies showed that the micelles self-assembled from HPGMAP(MEO2MA-co-OEGMA-co-RhBAMA)ns were thermoresponsive, and the micelles have different fluorescence intensity at different pH. In addition, DOX could be encapsulated by HPGMAP(MEO2MA-co-OEGMA-co-RhBAMA)n upon micellization and released upon adding GSH into the micelle solution. Temperature also affected the drug release. Cell culture assay indicated that these polymers had little cytotoxocity.5. Glucose-based hyperbranched star copolymers HPDMAEMA(PMAG1c)ns were obtained by deprotection of HPDMAEMA(PMA1pGlc)ns, which were synthesized by RAFT polymerization of MAlpGlc using HPDMAEMA as macro RAFT agnet. HPDMAEMA(PMAG1c)n self-assembled into various morphologies at different pH. After the addition of Con A, the specific binding between Con A and PMAG1c block resulted in the Con A-crosslinked aggregates. However, the resultant aggregates disassembled by adding free D-glucose because that the binding of PMAGlc and Con A was replaced by much stronger binding of D-glucose and Con A. In addition, the cytotoxicity of the HPDMAEMA(PMAGlc)n micelles was much lower than that of25k PEI.