Supramolecular Self-Assemblies Of Water-Soluble Stimuli-Responsive Block Copolymers And Their Nanostructural Fixation

Double hydrophilic block copolymers (DHBCs) were composed of two or more blocks. In dilute aqueous solution, the copolymer chains can self-assemble into two or more distinct micelles structure in the absence of any organic cosolvent. In each case, subjected to physical or chemical transformations, one of the blocks of DHBCs can be selectively rendered water-insoluble, while the other block still remains well-solvated to stabilize the formed colloidal aggregates. Compared with amphiphilic block copolymers, DHBCs provide enhanced structural versatility and additional aggregation modes, and the conformation of double hydrophilic block copolymer chains was different with that of free homopolymer chains in aqueous solution. These unique properties could be used in potential application. So we mainly discuss the synthesis, characterization and properties in aqueous solution of novel double hydrophilic block copolymers and study the conformation changes of DHBCs chains on the surface of a hydrophobic core in my former part of dissertation.However, the practical applications of various self-assembled aggregates of DHBCs were limited by their structural instability upon dilution or changes of external conditions. The approaches of core cross-linking (CCL) or shell cross-linking (SCL) of micelles were then developed to maintain their structural integrity. In my latter part of dissertation, we studied the DHBCs micelles' fixation using various methods, such as click chemistry and UV-induced cross-linking etc. The dissertation includes five parties as follows:1. We prepared poly(styrene-n-N-isopropylacrylamide) (PS-b-PNIPAM) diblock copolymer via reversible addition-fragmentation transfer (RAFT) polymerization. The resultant diblock copolymer can self-assemble into micelles consisting of PS cores and densely grafted PNIPAM brush as the shells. The thermoresponsive phase transition behavior of the micelles is characterized in detail by a combination of dynamic and static laser light scattering (LLS), micro-differential scanning calorimetry (micro-DSC), and excimer fluorescence techniques. All of these measurements support the conclusion that PNIPAM brush densely grafted at the surface of hydrophobic PS core exhibits double thermal phase transition behavior. The inner part of PNIPAM brush collapses first at lower temperatures (< 30℃), while above 30℃the outer part of PNIPAM brush start to collapse. Then we studied the double phase transition behavior of three-layer nanostructures with double thermoresponsive shells. Successive RAFT polymerization of NIPAM and 2-(dimethylamino)ethyl methacrylate (DMA) or DMA and NIPAM were conducted using PS macroRAFT agent. The PS-b-PNIPAM-b-PDMA and PS-b-PDMA-b- PNIPAM triblock copolymers can self-assemble into PS-core micelles, which possess a three layer 'onion-like' structure, with PDMA and PNIPAM blocks forming the inner layers or outer coronas. Using above measurements, we can concluded that PS-b-PNIPAM-b-PDMA triblock copolymer micelles have the double phase transition behavior, while PS-b-PDMA-b-PNIPAM have only one phase transition behavior.2. We synthesized poly(ethylene glycol-b-methacrylic acid) (PEG-b-PMAA)diblock copolymers with three different polymerization degree of PMAA blocks. The diblock copolymers molecularly dissolve in alkaline pH, and could form aggregates in acidic pH solution for the hydrogen-bonding formation between PEG and PMAA blocks. Then we study the pH-induced the hydrogen-bonding complex kinetics using stop-flow techniques. We find that hydrogen-bonding between the PEG and PMAA blocks resulted the formation of very larger aggregates in the first tens seconds, and followed a very slower equilibrium process. We also reported a "trinity" of micellar aggregates formed by poly(ethylene glycol-b-methacrylic acid-b-(2-diethylamino) ethyl methacrylate) (PEG-b-PMAA-b-PDEA) triblock copolymers in aqueous solution by simply adjusting the solution pH at ambient temperatures. The driving forces for forming these three types of micelles were hydrophobic interactions, interpolyelectrolyte complexation, and hydrogen-bonding, respectively. The hydrogen-bonded PEG/PMAA micellar aggregates formed at low pH; the PMAA/PDEA interpolyelectrolyte micelles formed at around the IEP were very sensitive to the ionic strength of the aqueous solution; conventional micelles with hydrophobic PDEA cores formed at high pH.3. We have demonstrated the successful synthesis of the SCL micelles prepared from the PEG-b-(CGMA-co-GMA)-b-DEA by UV-induced cross-linking reaction. The resulting SCL micelles exhibited reversible swelling/shrinking behavior on varying the solution pH. The effect of varying the PCGMA molar contents on the structure stability and pH-dependent (de)swelling of the SCL micelles was studied in detail. It was found that the SCL micelles at high degree of cross-linking exhibit excellent colloidal stability to external pH changes.4. Well-defined PDEA-b-PDMAr-b-PNIPAM triblock copolymer was successfully synthesized via atom transfer radical polymerization (ATRP). The triblock copolymer can self-assemble into PDEA-core micelles at alkaline pH and room temperature. Novel shell cross-linked micelles with pH-responsive PDEA cores and thermo-sensitive PNIPAM coronas in aqueous solution were then fabricated by cross-linking the inner PDMA shells of the PDEA-core micelles. These SCL micelles can act as drug nanocarriers: loading the DEA cores with a hydrophobic drug, followed by changing of solution pH and temperature, the drug release rate of the drug-loaded SCL micelles could be dually controlled.5. Combing the living radical polymerization and click chemistry, we report the facile fabrication of core cross-linked (CCL) micelles via click chemistry, which was starting from a well-defined thermoresponsive double hydrophilic diblock copolymer (DHBC) containing reactive azide moieties in the thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) block. Two approaches were attempted, and in both cases the obtained CCL micelles possess thermo-tunable core swellability. Then well-defined multi-responsive (pH and temperature) four-layer nanoparticles were fabricated from shell cross-linked (SCL) micelles with core-shell-corona microstructures bearing surface alkynyl groups via "click" chemistry. The SCL micelles with surface functionalized click group and pH-responsive cores were prepared from an alkynyl terminally functionalized POEGMA-b-PDMA-b-PDEA triblock copolymer synthesized via ATRP technique by one-pot method using an alkynyl initiator. After the click reaction of the SCL micelles and azide-terminus PNIPAM homopolymer, the novel PNIPAM-functionalized SCL micelles (SCL-PNIPAM) with pH-responsive cores and outer thermosensitive coronas were prepared, which was investigated act as excellent candidate of nanosized drug delivery vehicles. Finally, two types of novel shell cross-linked micelles in aqueous solution were prepared from these remarkable PMEO₂MA-b-P(DMA-co-QDMA)-b-PDEA triblock copolymers by cross-linking the inner P(DMA-co-QDMA) shell of micelles upon the addition of diazide tetra (ethylene glycol) derivative in the presence of copper catalyst using click chemistry.