Synthesis of Shell Cross-Linked Micelles with pH-Responsive Cores Using ABC Triblock Copolymers

Abstract

A series of well-defined poly[(ethylene oxide)-block-2-(dimethylamino)ethyl methacrylate-block-2-(diethylamino) methacrylate] (PEO−DMA−DEA) triblocks were synthesized by successive ATRP polymerization of DMA and DEA monomers using PEO-based macroinitiators of different molecular weights. These triblock copolymers dissolved molecularly in aqueous solution at low pH; on addition of NaOH, micellization occurred at pH 7.1 to form three-layer “onionlike” micelles comprising DEA cores, DMA inner shells, and PEO coronas. Above pH 7.3, dynamic light scattering studies indicated unimodal, near-monodisperse populations, with mean micelle diameters of 27−84 nm depending on block compositions (for PEO113 triblock copolymers) and polydispersities typically less than 0.10. The average hydrodynamic diameter 〈D h〉 of the micelles decreased as the solution pH was increased from pH 7.3 to pH 9.0, indicating that the micelles become more compact due to deprotonation of the tertiary amine residues in the DMA and DEA blocks. 1H NMR studies supported a three-layer micelle structure and also revealed changes in the hydrophilicity of the DMA chains in the inner shell during cross-linking, which was achieved by adding the bifunctional alkyl iodide, 1,2-bis(2-iodoethoxy)ethane (BIEE). Selective quaternization of the DMA residues by the BIEE leads to increased hydrophilicity and colloid stability for the shell cross-linked (SCL) micelles. The minimum amount of BIEE required to “lock-in” the micellar structure depended on the thickness of the PEO corona: shorter PEO chains led to enhanced cross-linking efficiency. At pH 8.5, the hydrodynamic diameter of un-cross-linked micelles increased rapidly above 40−50 °C due to the LCST behavior of the neutral DMA chains in the inner shell. In contrast, the dimensions of the SCL micelles in dilute aqueous solution are independent of temperature. These SCL micelles exhibit reversible swelling on varying the solution pH. At low pH, the DEA cores become protonated and hence hydrophilic. The effect of varying the block composition and the target degree of cross-linking on the structural stability and pH-dependent (de)swelling of the SCL micelles was systematically studied. Longer DEA blocks and lower target degrees of cross-linking led to increased swellability, as expected.

Double Hydrophilic Block Copolymer Monolayer Protected Hybrid Gold Nanoparticles and Their Shell Cross-Linking

“…30 min, these droplets disappeared and a homogeneous solution was formed; the mixed solution was stirred at pH 9 for 3 days at room temperature. As reported previously, 42 for the shell cross-linking of ABC triblock copolymer micelles, the actual degree of quaternization increases monotonically with the target degree of quaternization, but the former is always significantly less than the latter. Figure 2 compares the hydrodynamic radius distributions, f(R h ), of the original citrate-capped gold nanoparticles, the noncross-linked core/shell hybrid gold nanoparticles, and the crosslinked core/shell hybrid gold nanoparticles at 20°C.…”

“…cross-linked micelles in high solids using an ABC triblock copolymer; 42 here the micellar core was replaced with a gold nanoparticle. Figure 3 shows plots of Γ versus q 2 for original gold nanoparticles, core-shell gold nanoparticles before shell crosslinking, and core-shell gold nanoparticles after shell crosslinking,respectively.…”

“…This is consistent with the covalent stabilization via quaternization with a bifunctional agent. 42 The cross-linking has a 2-fold effect on the hybrid nanoparticles: first, quaternization suppresses the LCST phase behavior of PDMA block and renders them permanently hydrophilic; second, cross-linking results in a covalently connected network surrounding the gold nanoparticles and there is no chance for the structural arrangement of diblock copolymer chains between different hybrid nanoparticles. Overall, the shell cross-linked hybrid core/shell gold nanoparticles exhibit excellent colloidal stability at elevated temperatures compared to that before cross-linking.…”

“…32 Since that seminal work, the field of covalent stabilization of micelles and vesicles has attracted increasing attention in recent years. [40][41][42][43][44][45][46][47] Just recently, Taton et al reported the preparations of core/ shell gold nanoparticles via the block copolymer self-assembly approach. 48 Citrate-capped gold nanoparticles were first made hydrophobic with the introduction of 1-dodecanethiol; they were then mixed with poly(syrene-block-acrylic acid) (PS-b-PAA) in dimethylformamide (DMF), which is a common solvent for both PS-b-PAA and 1-dodecanthiol stabilized gold nanoparticles.…”

Synthesis and self-assembly of poly(ethylene oxide)-b-poly (2-hydroxyethyl methacrylate)

“…In particular, HEMA can be successfully polymerized with the molecular weight distributions ranging from 1.1 to 1.5 in both silyl-protected [5] and unprotected forms [6][7][8][9][10]. PEO-Br macroinitiator has been widely used in atom transfer radical polymerization [11][12][13]. Thus PEO-b-PHEMA double hydrophilic block copolymer can be synthesized using this method.…”