Synthesis And Properties Of Photoliable Hyperbranched Graft Copolymers And Comblike Block Copolymers

In polymer science, synthesis and poperties of stimuli-responsive polymers have attracted much attention since they can exhibit sharp responses to the environmental changes and physicochemical properties different from their linear analogues. Among various stimuli such as temperature, redox, light and p H, light is regarded as the most elegant and non-invasive trigger that is easy to manipulate in a spatiotemporal manner and insusceptible to physiological parameters. With the rapid development of “living”/ controlled polymerization techniques, many types of methods have been developed to prepare nonlinear copolymers with controllable structure and versatile functions. More recently, increasing attention has been paid to synthesis and properties of photosensitive polymers with a potential as smart nanocarriers for biological treatment. This study aims at facile synthesis and properties of novel photocleavable hyperbranched graft and block graft copolymers with o-nitrobenzyl(ONB) moieties by some techniques such as self-condensing vinyl polymerization(SCVP), reversible addition-fragmentation chain transfer(RAFT) polymerization and ring-opening polymerization(ROP). In addition, their structure-properties relationship and potential application in smart drug release were investigated. The main contents are listed as follows.The research in Part one aimed at synthesis and properties of novel photocleavable dendritic-unit-bridged hyperbranched graft copolymers(DHGCs) with oligomeric branches composed of poly(ethylene glycol) methyl ether acrylate(PEGA) units, linear poly(ε-caprolactone)(PCL) grafts and o-nitrobenzyl ester(ONBE) moieties in the dendritic unit. RAFT copolymerization of 3-((2-acryloyloxymethyl-2-hydroxymethyl) propionyloxy) methyl-2-nitrobenzyl 4-cyano-4-(phenylcarbonothioylthio)pentanoate(ANCP) and PEGA afforded hyperbranched poly(ANCP-co-PEGA)(abbreviated as PAP), and followed by CL polymerization to achieve PAP-g-PCL. 1H NMR and GPC-MALLS results confirmed the target copolymers had controlled molecular weight and relative low polydispersity(PDI = 1.2-1.4). Upon photo-cleavage, hyperbranched PAP was converted into linear polymers, and PAP-g-PCL was readily degraded into mixtures of linear, star and graft polymers. With increasing UV irradiation time, the PAP-g-PCL micelles were gradually evolved into vesicles and multicompartment vesicles since photo-triggered cleavage and reaggregation were dynamically performed. Upon normal and on-demand UV irradiation, the release kinetics for controlled release of Nile red from copolymer aggregates could be tuned in a wide range, revealing the great potential in smart drug delivery systems. Without UV irradiation, the normalized fluorescence intensity(NFI) of Nile red gradually decreased with extended time and dropped to about 0.688 at 12 h. Under 1.0 min UV irradiation, the NFI value was dropped to about 0.417 at 12 h. As five times of 1.0 min UV irradiation were individually applied at a particular time, the NFI value was dropped to about 0.235 at 12 h. This study affords a general approach to construct functional DHGCs and their derivatives, which can act as a versatile platform to explore the special properties and applications of novel macromolecular architecture in smart nanomaterials.The research in Part two aimed at synthesis and properties of novel photocleavable BAB-type linear-comblike-linear triblock copolymer, in which A was ONB-midfunctionalized comblike block with PEG and PCL grafts, and B was PNIPAM segment. The mixture of poly(ethylene glycol)-2-hydroxymethyl methyl ether acrylate(PEGHA, Mn = 510 g mol-1, 42mol%) and poly(ethylene glycol) methyl ether acrylate(PEGA) was synthesized, and then the target copolymer was synthesized by three step reactions. RAFT copolymerization of PEGHA and PEGA mediated by 1,3-di((4-cyano-4-(phenylcarbono thioylthio)valeryloxy)methyl)-2-nitrobenzene(DCPNB) afforded poly(PEGA-co-PEGHA)(abbreviated as PPPHA), and followed by RAFT chain extension polymerization of N-isopropylacrylamide(NIPAM) to generate PNIPAM-b-PPPHA-b-PNIPAM triblock copolymer(P2). On this basis, a subsequent CL polymerization was performed to give PNIPAM-b-[PPPHA-g-PCL]-b-PNIPAM(P3). P3 had controlled molecular weight and low polydispersity(PDI = 1.12), evident from 1H NMR and GPC-MALLS results. As thermo and UV irradiation stimuli were applied, the polymeric aggregates converted from spherical micelles into multicompartment micelles, vesicles, and multicompartment vesicles. As anticancer drug paclitaxel(PTX) was loaded into P3 micelles, the drug loading content and drug loading efficiency were 7.22% and 36.1%, respectively. The cumulative release of PTX from aggregates at 24 h was 18.3% at 25 oC without external stimuli. At 37 oC, the cumulative releases at 24 h were 26.6%(lack of light irradiation and additive), 39.5%(1.0 m M β-CD), 51.4%(1.0-min UV) and 70.2%(1.0 m M β-CD + 1.0-min UV). These results revealed that fast and efficient drug releases could be performed as external stimuli were applied, and thus the polymeric micelles have a great potential in smart drug delivery systems.In summary, this study was primarily focused on facile synthesis of nonlinear copolymers with photoliable ONB moieties which could act as precursors to construct photosensitive nanocarriers for smart drug delivery. With the addition of external stimuli, the morphologies of polymeric aggregates varied in a wide range. Our study can not only enrich the synthetic method of photo-responsive topological polymers but extend their applications in smart biomedical materials. Moreover, the resultant dendritic-unit-bridged hyperbranched graft copolymers belong to a novel subclass of graft copolymers, which are expected to act as an important member of nonlinear polymers.