Block And Branched Copolymers: Synthesis, Self-assembly And Drug Delivery

Polymer nanomaterials have been widely used in the fields of medicine and industry, due to their unique chemical structures and properties. Polymer nanomatericals with different morphologies have attracted great attention due to their special characters. In this dissertation, we prepared a series of responsive polymers nanomaterials via reversible addition-fragmentation chain transfer (RAFT) polymerization and investigated their properties and applications in drug delivery. The primary results acquired are listed as follows:1. Reduced-and pH-responsive amphiphilic branched star copolymers BP(DMAEMA-co-MAEBA-co-DTDMA)(PMAGP), (BSP-H) were prepared via RAFT polymerization. DOX was linked onto the branched star polymers with the imine bond. The micelles were self-assembled from amphiphilic branched star copolymers prodrug (BSP-H-DOX). DOX could be released from polymer prodrug micelles under acidic condition, with existance of DTT the release rate could be accerelate. The amphiphilic branched star copolymers is low toxicity. The galactose functional groups in the PMAGP block have specific interaction with HepG2 cells. So the polymer micelles could be an efficient drug celivery system which targeted the HepG2 cells.2. A series of polymer nanomaterials with different morphologies were prepared via RAFT polymerization of MAEBA using PHPMA as macro-RAFT agent. The morphology of polymer nanpmaterials could be protected by cross-linked with 1, 4-butanediamine. The nanomaterials after cross-linked is stable in their good solvent such as DMF. The sizes of spheres micelles and nanowires became smaller after cross-linked, but the size of vesicles became bigger after cross-linked. The protected polymer nanomaterials is stable in nutral condition but degraded in acidic condition, which has potential application in organic synthesis, wastewater treatment and drug delivery3. To study influence of the self-assembled morphologies on the drug delivery, four different nano-objects, spheres, nanorods, nanowires and vesicles were successfully prepared via alcoholic RAFT dispersion polymerization of MAEBA using poly(N,N’-dimethylaminoethyl methacrylate) as a macro chain transfer agent (macro-CTA) for the first time. The anti-cancer drug, doxorubicin (DOX) was conjugated onto the core polymers of nano-objects through condensation reaction of aldehyde groups in the PMAEBA with primary amine groups of the DOX. Because the aromatic imine is stable under neutral conditions, but is cleaved at weakly acidic solutions, the in vitro release of DOX from the DOX-loaded nano-objects was investigated in the different acidic solutions. All the block copolymer nano-objects show very low cytotoxicity to Hela cells, but the DOX-loaded nano-objects reveal different cell viability and their IC50 increase as the following order:Nanorods-DOX< Vesicles-DOX< Spheres-DOX. Endocytosis tests demonstrate that the internalization of Vesicles-DOX by the Hela cells is faster than that of the Nanorods-DOX, and the Spheres-DOX are the slowest to internalize among the studied nano-objects. Relatively more nanorods localized in the acidic organelles of the Hela cells lead to faster intracellular release of the DOX, so, the IC50 of nanorods is lower than that of Vesicles-DOX.4. In our report, we design a novel drug delivery system of polymer prodrug covered silver nanoparticles (P(HEO2MA-co-MACPT)@AgNPs), which the drug linked on the polymer with a new kind of acidic-sensitive covalent bond of β-thiopropionate bond. The drug delivery system has been successively prepared vis RAFT random copolymerization of 2-(2-hydroxyethoxy)ethyl methacrylate (HEO2MA) and methacryloyloxy-3-thiahexanoyl-camptothecin (MACPT), the copolymers reacted onto the surface of AgNPs through Ag-sulfide interactions. While the distance between AgNPs and CPT close enough, the fluorescence of CPT quenched. The drug release curves was obtain under acidic condition, with the release of CPT, the fluorescence of CPT recovered. What’s more, the drug delivery system can successfully transport and release the CPT in cancer cell.5. Amphiphilic blcok copolymers prodrug P(HEO2MA)-b-P(DHLA-CPT) were synthesized by RAFT polymerization. Micelles was formed by Amphiphilic blcok copolymers prodrug and the size is 50 nm. The drug can be released from the prodrug micelles at pH of 6.0 but no release at pH 7.4. Cell culture assay indicated that the polymers had little cytotoxicity. The CLSM photo shown that the micelles can be easily internalized by Hela celles.