Self-assembly and gold nanoparticle cross-linking of stimuli-responsive block copolymers synthesized by reversible addition-fragmentation chain transfer polymerization

Adam Eugene Smith


The ability of amphiphilic block copolymers to self-assemble into various morphologies in aqueous solution in response to specific stimuli has attracted widespread interest for potential applications as targeted drug delivery and diagnostic vehicles. Stimuli-responsive block copolymers afford a facile method for tuning the hydrophilic mass fraction to provide access to various solution morphologies. Reversible additionfragmentation chain transfer (RAFT) polymerization provides the ability to prepare stimuli-responsive block copolymers while maintaining precise control over the macromolecular characteristics (molecular weight, copolymer composition, functionality, etc.) that dictate nanostructure morphology. This work may be divided into four sections. In the first section the synthesis and thermally-repsonsive self-assembly behavior of poly[2-(dimethylamino)ethyl methacrylate73 -block-(N -isopropylacrylamide) 99 ] (P(DMAEMA73 -b -NIPAM99 )) is discussed. At elevated temperatures, P(DMAEMA73 -b -NIPAM 99 ) exhibited a reversible vesicle formation in aqueous solution. Simply mixing a pH 7.4 vesicle solution at 50°C with a solution of NaAuCl 4 led to the formation gold nanoparticle (AuNP)-"decorated" vesicles. The second study details the preparation of a series of DMAEMA and NIPAM block copolymers. Controlling block lengths, solution pH, and NaCl concentration to elicit changes in the hydrophilic mass fraction resulted in specific morphological changes upon thermally-induced assembly. At 68 wt% DMAEMA, P(DMAEMA 165 -b-NIPAM102 ) self-assembled into simple core-shell micelles (58 nm). Increasing the DMAEMA content to 48 wt% lead to a mixture of spherical micelles (78 nm) and worm-like micelles (D=50-100 nm, L=400-500 nm). Further increasing to 36 wt% DMAEMA produced vesicular structures (179 nm). The associated nanostructures were subsequently shell cross-linked above the critical aggregation temperature via the in situ formation of AuNPs to yield assemblies with long term aqueous stability. In the third section the reversible gold nanoparticle cross-linking of polymeric vesicles derived from a RAFT-generated, thermally-responsive diblock copolymer, P(DMAEMA165 -b -NIPAM435 ), is reported. Vesicles were first self-assembled above the critical aggregation temperature of the diblock copolymer and subsequently cross-linked by the in situ AuNP formation in the tertiary amino-functionalized vesicle shell. The cross-linking was then reversed by the addition of the thiols, cysteamine or a thiolated poly(ethylene glycol) (PEG-SH), capable of inducing a ligand exchange on the surface of the AuNP to free the bound polymer chains. The sizes of the thiol-stabilized AuNPs produced during the ligand exchange with both cysteamine and PEG-SH were found to be ∼ 8 nm. In the fourth study, dually-responsive block copolymers of ( N,N -diethylaminoethyl methacrylate and NIPAM capable of "schizophrenic" aggregation in aqueous solution were synthesized via aqueous RAFT polymerization. The nanoassembly morphologies, dictated by the hydrophilic mass fraction, were systematically controlled by the polymer block lengths, solution pH, and temperature. Both P(DEAEMA 98 -b -NIPAM 209 ) (52.5 wt% NIPAM) and P(DEAEMA98 -b -NIPAM 392 ) (70.8 wt% NIPAM) self-assembled into PDEAEMA-core, PNIPAM-shell spherical micelles (∼ 42 and 52 nm, respectively) at temperatures below the lower critical solution temperature (LCST) of PNIPAM and at solution pH values greater than the pKa of PDEAEMA. The two block copolymers, however, display quite different temperature-responsive behavior at pH < 7.5. At elevated temperatures (> 42°C) P(DEAEMA98 - b -NIPAM209 ) formed spherical micelles (∼ 52 nm) with hydrophobic PNIPAM cores stabilized by a hydrophilic PDEAEMA shell. By contrast, P(DEAEMA98 -b -NIPAM392 ) assembled into vesicles (∼ 200 nm) above 38°C.