Synthesis And Properties Of Stimuli-Responsive Multicomponent Star Copolymers

Synthesis and properties of stimuli-responsive polymers have attracted much attention in polymer science recently. The progress in controlled polymerization techniques and coupling chemistry has efficiently promoted the development of complex macromolecular architectures with multiple stimuli responsivenesses. Much attention has been paid on synthesis and properties of linear polymers, and star polymers also attract increasing interest due to their unique topology and physicochemical properties. At present, the examples of multi-stimuli-responsive miktoarm star copolymers are relatively scarce, and it is very important to adjust the molecular parameters and versatile properties toward multipurpose applications. This study aims at synthesis of multi-sensitive ABC and ABCD-type miktoarm stars by combination of controlled polymerization and linking reaction, the influence of external stimuli on topological transformation and properties, and potential application in smart biomedical materials. The main contents are listed as follows.The study in Part one aimed at synthesis and properties of an acid-labile dual-sensitive ABCD star quaterpolymers comprising thermo-sensitive poly(N-isopropylacrylamide)(PNIPAM, A), p H-responsive poly(2-diisopropylaminoethyl methacrylate)(PDPA, B), biodegradable poly(ε-caprolactone)(PCL, C), and biocompatible acetal-linked poly(ethylene glycol)(a PEG, D) segments. Starting from prop-2-ynyl 3-(5-cyano-5-phenylthiocarbonylsulfanyl)pentanoyloxy-2-(2-bromo-2-methylpropanoylox y)methyl-2-hydroxymethylpropionyloxymethyl-2-methylpropanoate(PCBP), successive multistep reactions involving RAFT polymerization of NIPAM, ATRP of DPA, and ROP of CL were performed to afford alkyne-core-functionalized ABC star terpolymer. Terminal azide-functionalized a PEG and alkyne-core-functionalized ABC star was subjected to copper(I)-catalyzed azide-alkyne cycloaddition(Cu AAC) reaction to generate the target star quaterpolymer. As evidenced by 1H NMR and GPC-MALLS, the resultant copolymers had well-defined structures, low polydispersity indices(PDI = 1.09-1.15). As different stimuli were applied, polymeric aggregates were liable to reassembly, and large compound micelles, flower-like micelles and small micelles could be formed. Doxorubicin-loaded copolymer aggregates exhibited accelerated drug release kinetics upon thermo and p H stimuli, and the maximum cumulative release could up to 56.1% in 48 h. The micellar system may hold a great promise for biomedical applications due to its relatively low cytotoxicity and stimuli-tunable release properties.The study in Part two aimed at synthesis and properties of novel miktoarm star PNIPAM-PCL-P(AA-co-HEDA)(ABC2) with cleavable disulfide moieties. 4-Cyano-4-phenylcarbonothioylthiopentyl-2-(2-bromo-2-methylpropanoyl)methyl-2-hydroxylmethy lpropanoate(CBHP) was synthesized and used to prepare PNIPAM-b-PCL copolymer. On this basis, ATRP of tert-butyl acrylate(t BA) and 2-(2-(2-hydroxyethyl)disulfanyl)ethyl acrylate(HEDA) was performed to afford PNIPAM-PCL-P(t BA-co-HEDA)(ABC1), and followed by selective hydrolysis to obtain PNIPAM-PCL-P(AA-co-HEDA)(ABC2). As evidenced by 1H NMR and GPC-MALLS, the resultant star copolymer had well-defined structure and low polydispersity(PD = 1.10). The ABC2 star could self-assemble into versatile morphologies involving spherical micelles and vesicles, and the hydrodynamic diameter and particle size distribution of aggregates were significantly affected by external stimuli such as p H, temperature and reduction. In the presence of external stimuli, in vitro release of DOX-loaded ABC2 aggregates were investigated. The maximum of increment of cumulative release at 24 h was 59.0%(37 oC, p H 5.3 + DTT), 43.7%(37 oC + DTT + p H 7.4), 37.1%(37 oC + p H 5.3), 27.0%(37 oC, p H 7.4) and 15.3%(25 oC, p H 7.4). These results revealed that DOX-loaded aggregates could exhibit stimuli-adjustable release kinetics, and they had a great potential as smart drug delivery vehicles.In summary, this study aims at synthesis and properties of novel miktoarm stars with cleavable moieties and stimuli-responsive segments. Multi-stimuli-responsive systems could be constructed by self-assembly or coassembly, and their self-assembly behaviors, topological transformations and physicochemical properties were strongly dependent on external stimuli such as temperature, p H and reductive condition. Some general methods to prepare multicomponent star copolymers with cleavable linkages were developed in this study, and the types of miktoarm star copolymers were enriched. Moreover, our study further extended the potential of star copolymers toward smart materials.