Synthesis, Self-assembly And Applications Of Functional Block Copolymers

With the development of controlled/"living" radical polymerization, many monomers have been introduced into the block copolymer system. Great progress has been achieved in synthesis and self-assembly of amphiphilic block copolymers, as well as its applications in drug delivery. However, there's still plenty of room for more smart and integrated drug carriers.In this dissertation, several diblock copolymers were synthesized via controlled/ "living" radical polymerization. Proper modifications and self-assembly offer the supermolecular polymeric micelles with various functions, such as pH, redox, thermal responsiveness as well as light stimuli. In summary, this dissertation includes the following four parts:Firstly, well-defined diblock copolymer ofpoly(ethylene oxide)-b-poly(tert-butyl methacrylate), PEO-b-PtBMA was synthesized via atom transfer radical polymerization (ATRP) using a PEO-based macroinitiator. Hydrazide group was obtained after treatment with trifluoroacetic acid and hydrazine modification, which can form acid labile hydrazone linker with adriamycin (ADR). The supermolecular polymeric micelles were obtained after self-assembly in water. The micelles were crosslinked using disulfide containing agent, which gave drug carriers with dual responsivenesses. The block copolymer and micelles were characterized using GPC, NMR, DLS as well as TEM. In-vitro experiment demonstrated that the obtained supermolecular polymeric micelles exhibiting "AND" logic gate for controlled release of ADRwith both pH and DTT (redox) as input stimuli signals, which mimic the tumor environment. While either of the two stimuli input signals or either one was turned off, the drug release would be dramatically suppressed.Secondly, well-defined amphiphilic diblock copolymer poly((N-(2-hydroxypropyl) methacrylamide)-b-poly(benzyl methacrylate) (PHPMA-b-PBnMA) with narrow molecular weight distribution was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization using cumyl dithiobenzoate (CDB) as chain transfer agent. The terminal dithioester was converted into carboxylic acid for aminated folic acid conjugation. The folate conjugated polymer self-assembled into micelles for ADR carriers. Fluorescence spectra were used to determine the critical micelle concentration (CMC) of the folic acid conjugated amphiphilic block copolymer. Dynamic light scattering (DLS) measurements revealed the high stability of the micelles with or without loading of the drug ADR. In vitro release experiment showed that the micelle encapsulated ADR was stable in a typical circulation condition and could be quickly released under acidic endosome pH.Thirdly, poly(N-isopiropylacrylamide)-b-poly(N-methacryloxysuccinimide) was synthesized via RAFT using S-1-Dodecyl-S'-(α(?)α(?)-dimethyl-α"-acetic acid) trithiocarbonate (DDAT) as chain transfer agent. The derivative polymer poly(N-isopropylacrylamide)-b-poly(methacrylate hydrazide) (PNIPAAm-b-PMAH) was thus obtained after reaction with hydrazine. The resulted double hydrophilic block copolymer (DHBC) had two segments responsive to pH and temperature, respectively. Schizophrenic micellization behavior of DHBC was observed. In aqueous, the polymer is soluble in water. At 20℃and pH= 12.0, the polymer self-assembled into micelles with PMAH as core and PNIPAAm as shell, while at 40℃and pH= 2.0, the polymer formed converted micelles with PMAH as shell and PNIPAAm as core. Besides, poly(para-nitrophenoxycarbonyloxyethyl methacrylate)-b-poly(N-isopropylacrylamide) was also synthesized using DDAT as chain transfer agent. After reaction with ethylenediamine, the functionliazed diblock polymer has strong green photoluminescence.Finally, poly(ethylene oxide)-b-poly(N-methacryloxysuccinimide) (PEO-b-PMASI) was obtained via ATRP. Poly(ethylene oxide)-b-poiy(methacrylate hydrazide) (PEO-b-PMAH) was obtained with hydrazine modification, which was merit for ADR conjugation. The polymer could form micelles in water,the cores of the micelles were cross-linked afterwardby o-nitrobenzyl group based diacid, which is light sensitive. The structure of the micelles was characterized by GPC, NMR, FT-IR, as well as UV-vis.