pH-responsive Self-assembly Behavior Research Articles

Effect of Hydrophilic Monomer Distribution on Self-Assembly of a pH-Responsive Copolymer: Spheres, Worms and Vesicles from a Single Copolymer Composition.

A series of copolymers containing 50 mol % acrylic acid (AA) and 50 mol % butyl acrylate (BA) but with differing composition profiles ranging from an AA‐BA diblock copolymer to a linear gradient poly(AA‐grad‐BA) copolymer were synthesized and their pH‐responsive self‐assembly behavior was investigated. While assemblies of the AA‐BA diblock copolymer were kinetically frozen, the gradient‐like compositions underwent reversible changes in size and morphology in response to changes in pH. In particular, a diblock copolymer consisting of two random copolymer segments of equal length (16 mol % and 84 mol % AA content, respectively) formed spherical micelles at pH >5, a mix of spherical and wormlike micelles at pH 5 and vesicles at pH 4. These assemblies were characterized by dynamic light scattering, cryo‐transmission electron microscopy and small angle neutron scattering.

PH-Driven Morphological Diversity in Poly[n-Butyl Acrylate-block-(2-(Dimethylamino)Ethyl Acrylate)] Amphiphilic Copolymer Solutions.

Amphiphilic poly[n-butyl acrylate-block-(2-(dimethylamino)ethyl acrylate)] (PnBA-b-PDMAEA) block copolymers are synthesized by the reversible addition fragmentation chain transfer polymerization process. The pH-responsive self-assembly behavior in aqueous media is studied by dynamic, static, and electrophoretic light scattering and cryogenic transmission electron microscopy (Cryo-TEM) at different pHs. In particular, the PnBA40 -b-PDMAEA60 copolymer (where subscripts denote %wt composition of the components) shows remarkable morphological transitions in aqueous solutions of varying pH values forming, among others, an unusual and novel hierarchical vesicular morphology, as indicated by Cryo-TEM results. The observed transitions are attributed to synergistic effects involving alterations of the protonation degree of the PDMAEA block, in conjunction with the specific composition of the copolymer and the softness of PnBA blocks, with cumulative drive changes in the packing parameter of the copolymer system and result in the formation of various unexpected morphologies by simple pH changes.

Synthesis, Self-Assembly, and Drug-Release Properties of New Amphipathic Liquid Crystal Polycarbonates.

New amphiphilic liquid crystal (LC) polycarbonate block copolymers containing side-chain cholesteryl units were synthesized. Their structure, thermal stability, and LC phase behavior were characterized with Fourier transform infrared (FT-IR) spectrum, 1H NMR, gel permeation chromatographic (GPC), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), polarizing optical microscope (POM), and XRD methods. The results demonstrated that the LC copolymers showed a double molecular arrangement of a smectic A phase at room temperature. With the elevating of LC unit content in such LC copolymers, the corresponding properties including decomposition temperature (Td), glass temperature (Tg), and isotropic temperature (Ti) increased. The LC copolymers showed pH-responsive self-assembly behavior under the weakly acidic condition, and with more side-chain LC units, the self-assembly process was faster, and the formed particle size was smaller. It indicated that the self-assembly driving force was derived from the orientational ability of LC. The particle size and morphologies of self-assembled microspheres loaded with doxorubicin (DOX), together with drug release tracking, were evaluated by dynamic light scattering (DLS), SEM, and UV–vis spectroscopy. The results showed that DOX could be quickly released in a weakly acidic environment due to the pH response of the self-assembled microspheres. This would offer a new strategy for drug delivery in clinic applications.

Synthesis of self-assemble pH-responsive cyclodextrin block copolymer for sustained anticancer drug delivery

Well-defined pH-responsive poly(e-caprolactone)-graft-β-cyclodextrin-graft-poly(2-(dimethylamino)ethylmethacrylate)-co-poly(ethylene glycol) methacrylate amphiphilic copolymers (PCL-g-β-CD-g-P(DMAEMA-co-PEGMA)) were synthesized using a combination of atom transfer radical polymerization (ATRP), ring opening polymerization (ROP) and “click” chemistry. Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR), and gel permeation chromatography (GPC). Then, the polymers could selfassemble into micelles in aqueous solution, which was demonstrated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The pH-responsive self-assembly behavior of these copolymers in water was investigated at different pH values of 7.4 and 5.0 for controlled doxorubicin (DOX) release, and these results revealed that the release rate of DOX could be effectively controlled by altering the pH, and the release of drug loading efficiency (DLE) was up to 88% (W/W). CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility, whereas the DOX-loaded micelles remained with high cytotoxicity for HeLa cells. Moreover, confocal laser scanning microscopy (CLSM) images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX. These results successfully indicated that pH-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release.

Molecular insights into the pH-induced self-assembly of CTAB/PPA system

Self-assembly systems of stimuli-responsive molecules possess the capability of altering its morphologies and properties when receiving external signals (variations in pH value, temperature, light, etc), which has generated emerging applications, and therefore, attracted great interests. However, revealing mechanisms of stimuli-induced self-assembly morphology transition is still in its infancy and experimentally challenging. In this work, we studied the pH-induced self-assembly of cetyltrimethylammonium bromide (CTAB) and potassium phthalic acid (PPA) mixtures by coarse-grained (CG) molecular dynamics (MD) simulation, aiming to give insights into the pH-responsive self-assembly behavior. We simulated the self-assembly of CTAB/PPA mixtures, and obtained spherical, rod-like, and threadlike micelles depending on pH value and PPA/CTAB ratio. Besides, we found that the length of rod-like micelles fluctuated with the increase of PPA/CTAB ratio, and that the self-assembling morphology shifted between rod-like and threadlike micelles when fixing the PPA/CTAB ratio at 4:6 and varying the pH value. With analyzing the net charge number around the CTAB micelles, the arrangement and distribution of CTAB and PPA molecules in micelles, we concluded that the electrostatic shielding and space location-obstruct of PPA play a key role in the pH-induced self-assembly. This work revealed molecular-level information and mechanisms of the pH-induced self-assembly of CTAB/PPA mixtures, which is expected to trigger further understanding and studies on pH-responsive self-assembly behavior.

Synthesis and pH-responsive self-assembly behavior of a fluorescent amphiphilic triblock copolymer mPEG-b-PCL-b-PDMAEMA-g-PC for the controlled intracellular delivery of doxorubicin

Schematic illustration of the pH-responsive self-assembly of a mPEG-b-PCL-b-PDMAEMA-g-PC copolymer with fluorescent coumarin units for controlling DOX release.

A pH-responsive and magnetically separable dynamic system for efficient removal of highly dilute antibiotics in water

In order to control the antibiotic-related crisis and reduce the negative impacts on the environment and human health, it is urgent to develop effective technologies to eliminate residual antibiotics in water. Herein, we successfully fabricated a novel, pH-responsive and magnetically separable dynamic system for micropollutant adsorption and oxidation degradation in graphene oxide (GO)/nanoscale zero-valent iron (nZVI) composite with macroscopic structure. The pH-responsive self-assembly behavior of GO/nZVI composite was explored. The macroscopic structure of GO/nZVI composite serves as an excellent adsorbent for antibiotic removal in water. The adsorption process is fast and highly efficient even in high salty and humic acid containing water under acid to neutral conditions. After removal antibiotics, GO/nZVI composite is conveniently separated by magnetic system and put into alkaline solution (pH > 9) for adsorbent regeneration. Interestingly, it is found that at pH > 9, GO/nZVI composite disassembles partly upon increasing pH values, leading to the elution of antibiotics for efficient antibiotics degradation by ozonization. More importantly, this pH-responsive GO/nZVI system exhibits high removal efficiency, high stability, reusability and easily separation, making it a promising method for treatment of water with micropollutants.

Synthesis, characterization and pH-Responsive self-assembly behavior of amphiphilic multiarm star triblock copolymers based on PCL, PDEAEMA, and PEG

A series of amphiphilic 4- and 6-armed star triblock copolymers based on poly(ɛ-caprolactone) (PCL), poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA), and poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) were designed and synthesized by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The continuous ARGET ATRP of DEAEMA and PEGMA was in situ monitored by react infrared spectroscopy (ReactIR) and showed good first-order kinetic characteristics. The molecular weights and chemical structures of the copolymers and their precursors were confirmed by gel permeation chromatography (GPC) and 1H NMR. The critical micelle concentration (CMC) values of the star copolymers in aqueous solution were extremely low (2.2–4.0 mg/L), depending on the architecture of the copolymers. The pH-responsive self-assembly behavior of the star copolymers in aqueous solution was investigated by a combination of dynamic light scattering (DLS), UV-vis spectrometry and scanning electron microscopy (SEM). When the pH values decreased from 10 to 3, no obvious fluctuation of the visible light transmittance of the micelle solutions was observed for lower polymer concentrations of 0.1 and 1 mg/mL, while sharp increase occurred at higher concentration of 10 mg/mL. The hydrodynamic diameters (D h ) of the micelle solutions appeared slight increase with the increase of concentration, and increased rapidly as the pH decreased from 10 to 4 followed by a slight decrease at pH 3. The effects of pH value on the zeta potentials exhibited almost the same tendency with the D h . This may due to the fact that the protonation of tertiary amine groups in DEAEMA can induce the swelling of micelles. The PCL and PDEAEMA contents and the topological structures (4- or 6-arm) showed significant influences on the pH-sensitivity of the micelles. Overall, the results demonstrated that the structures and pH-sensitivity of these amphiphilic copolymers could be well-controlled and their self-assembled micelles are promising carriers for delivery of anticancer hydrophobic drugs.

PH responsive MWCNT–star terpolymer nanohybrids

We present a unique multisegmented, heteroarm star block terpolymer that can be used as an effective dispersing agent for multiwalled carbon nanotubes in aqueous media. The (polystyrene)22(poly(2-vinylpyridine)-b-poly(acrylic acid))22, PS22(P2VP-b-PAA)22, star terpolymer exhibits a pH responsive self-assembly behavior in aqueous solution, due to the ampholytic nature of its diblock copolymer arms. Depending on the pH of the medium, two different self-assemblies were observed. At a low pH (pH 2), core–shell unimolecular micelles, with a hydrophobic PS core and P2VP, PAA segments in the shell, as well as multicore large compound micelles were formed. At pH 8.5, the star was transformed from a bis-hydrophilic into a bis-hydrophobic state, leading to a network-like intermicellar assembly. This star terpolymer was capable of dispersing MWCNTs, through non-covalent interactions, thus leading to stable MWCNT–star nanohybrids in water. More importantly, the resulted MWCNT–star nanohybrids adopted the “smart” pH responsive properties of the physisorbed stars, i.e. the nanohybrids can be positively or negatively charged at low and high pH respectively, while at an intermediate pH window, phase separation occurs due to neutralization of the oppositely charged segments.

Synthesis and Self-Assembly Behavior of Four-Arm Poly(ethylene oxide)-b-poly(2-(diethylamino)ethyl methacrylate) Star Block Copolymer in Salt Solutions

A well-defined block copolymer consisting of four-arm poly(ethylene oxide)-b-poly(2-(diethylamino)ethyl methacrylate) (four-arm PEO56-b-PDEAEMA74) was synthesized by atom transfer radical polymerization. The pH-responsive self-assembly behavior was examined by potentiometric titration, surface tensiometry, laser light scattering, and transmission electron microscopy over the course of dissociation by the addition of a base or acid. The apparent hydrodynamic radius (Rh) of the micelle increased from 21 to 56 nm when the degree of protonation of the amine groups was increased from 0 to 0.5 in 0.01 M NaCl solution. In higher concentration NaCl solution, the micelle shrank due to the electrostatic charge screening of the protonated DEAEMA groups. At low pH, the micelles dissociated into unimers.

PH-responsive self-assembly of carboxyl-terminated hyperbranched polymers

This work has presented a typical example to reveal the great influence of the terminal groups on the self-assembly of hyperbranched polymers. The hyperbranched polymers with hydroxyl terminal groups (HBPO-OH) were hydrophobic and precipitated in water, however, they displayed a pH-responsive self-assembly behavior when the terminal groups were replaced by carboxyl groups. The obtained carboxyl-terminated hyperbranched polymers (HBPO-COOH) existed as unimolecular micelles at high pH (12.21) due to the ionization of carboxyl groups, while the polymers aggregated into multimolecular micelles from 10 to 500 nm with the decrease of pH as a result of the partial protonation of the carboxyl groups. The size of the obtained micelles depended strongly on the solution pH - the lower the pH, the bigger the micelles. TEM, DLS, ATR-FT-IR, (1)H NMR and AFM measurements substantiated that the multimolecular micelles were formed by the secondary aggregation of unimolecular micelles driven by the hydrogen bonding interaction depending on the solution pH.