Core-forming Block Research Articles

Poly(Pentafluorophenyl Methacrylate)-Based Nano-Objects Developed by Photo-PISA as Scaffolds for Post-Polymerization Functionalization.

The preparation of a functional fluorine-containing block copolymer using reversible addition-fragmentation chain-transfer dispersion polymerization in DMSO as a "platform/scaffold" is explored. The nanostructures, comprised of poly(ethyleneglycol)-b-poly(pentafluorophenyl methacrylate) or PEG-b-P(PFMA), are formulated via photo-initiated polymerization-induced self-assembly (PISA) followed by post-polymerization modification using different primary amines. A combination of light scattering and microscopy techniques are used to characterize the resulting morphologies. It is found that upon varying the degree of polymerization of the core-forming block of PFMA, only uniform spheres (with textured surfaces) are obtained. These nanostructures are subsequently modified by cross-linking using a non-responsive and a redox-responsive diamine, thus imparting stability to the particles in water. In response to intracellular glutathione (GSH) concentration, destabilization of the micelles occurs as evidenced by dynamic light scattering. The well-defined size, inherent reactivity of the nanoparticles toward nucleophiles, and GSH-responsiveness of the nanospheres make them ideal scaffolds for drug delivery to intracellular compartments with reductive environments.

Toward Uniform Nanofibers with a π-Conjugated Core: Optimizing the “Living” Crystallization-Driven Self-Assembly of Diblock Copolymers with a Poly(3-octylthiophene) Core-Forming Block

Crystalline poly(3-alkylthiophene) (P3AT) nanofibers are promising materials for a myriad of device applications, but nanofiber length control and colloidal stability are difficult to achieve. We report an in-depth study of the solution self-assembly of regioregular poly(3-octylthiophene)-b-poly(dimethylsiloxane) (P3OT-b-PDMS) diblock copolymers with a crystallizable π-conjugated core-forming block. Use of the “living” crystallization-driven self-assembly (CDSA) seeded-growth method in solvents selective for PDMS allowed access to relatively low length dispersity, colloidally stable P3OT-b-PDMS fiber-like micelles with a crystalline, tape-like P3OT core, a PDMS corona, and lengths up to ca. 600 nm under optimized conditions. Significantly, the presence of a small percentage of common solvent and the use of slightly elevated temperature (35 °C) were found to enhance the length control. Analogous studies for P3OT-b-PS (PS = polystyrene) suggest that solvent composition and temperature represent key paramete...

Ketone-Functionalized Polymer Nano-Objects Prepared via Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA) Using a Poly(diacetone acrylamide)-Based Macro-RAFT Agent.

Herein, ketone-functionalized diblock copolymer nano-objects are prepared by photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of tert-butyl acrylate (tBA) using a poly(diacetone acrylamide) (PDAAM)-based macromolecular RAFT (macro-RAFT) agent in ethanol/water (60/40, w/w) at room temperature. A high polymerization rate is observed via the exposure of visible light (λmax = 405 nm, 0.45 mW cm-2 ) with near quantitative monomer conversion being achieved within 60 min. A morphological phase diagram is constructed by changing the degree of polymerization (DP) of PtBA and the monomer concentration. The morphologies of polymer nano-objects are further tuned by incorporating isobornyl acrylate (IBOA) into the core-forming block. The ketone-functionalized diblock copolymer nano-objects can be shell-cross-linked by reacting with a diamine. Finally, the shell-cross-linked polymer nano-objects are further hydrolyzed and employed as a template for the synthesis of silver composites.

Molecular Insight into Drug-Loading Capacity of PEG-PLGA Nanoparticles for Itraconazole.

Nanoparticles made of amphiphilic block copolymers comprising biodegradable core-forming blocks are very attractive for the preparation of drug-delivery systems with sustained release. Their therapeutic applications are, however, hindered by low values of the drug-loading content (DLC). The compatibility between the drug and the core-forming block of the copolymer is considered the most important factor affecting the DLC value. However, the molecular picture of the hydrophobic drug-copolymer interaction is still not fully recognized. Herein, we examined this complex issue using a range of experimental techniques in combination with atomistic molecular dynamics simulations. We performed an analysis of the interaction between itraconazole, a model hydrophobic drug, and a poly(ethylene glycol)-poly(lactide- co-glycolide) (PEG-PLGA) copolymer, a biodegradable copolymer commonly used for the preparation of drug-delivery systems. Our results clearly show that the limited capacity of the PEG-PLGA nanoparticles for the accumulation of hydrophobic drugs is due to the fact that the drug molecules are located only at the water-polymer interface, whereas the interior of the PLGA core remains empty. These findings can be useful in the rational design and development of amphiphilic copolymer-based drug-delivery systems.

CO2 -Breathing Polymer Assemblies via One-Pot Sequential RAFT Dispersion Polymerization.

ABC triblock copolymer assemblies with reversible "breathing" behaviors based on poly[oligo(ethylene glycol) methyl ether methacrylate]-b-poly(benzyl methacrylate)-b-poly[2-(diethylamino)ethyl methacrylate] (POEGMA-b-PBnMA-b-PDEA) are fabricated via one-pot sequential reverisble addition-fragmentation chain transfer dispersion polymerization. Using a POEGMA as the macromolecular chain transfer agent, chain extension with BnMA and DEA is conducted in ethanol, where PBnMA acts as the core-forming block, and the PDEA block endows the solvophilicity and CO2 -responsiveness. With the increment of the DP of PBnMA, the morphology of the assemblies evolves from spheres to worms, and to vesicles, while it degenerates from conglutinated vesicles to spheres as the DP of PDEA increases. After replacing ethanol with water, the morphologies of these assemblies remain unchanged, while their size decreases due to the collapse of the hydrophobic PDEA chains. Interestingly, due to the protonation and deprotonation of PDEA blocks, both the spheres and vesicles manifest a reversible expansion/shrinkage upon alternative CO2 /Ar stimulation, exhibiting distinctive breathing feature.

Mechanistic Insights into Diblock Copolymer Nanoparticle-Crystal Interactions Revealed via in Situ Atomic Force Microscopy.

Recently, it has become clear that a range of nanoparticles can be occluded within single crystals to form nanocomposites. Calcite is a much-studied model, but even in this case we have yet to fully understand the details of the nanoscale interactions at the organic-inorganic interface that lead to occlusion. Here, a series of diblock copolymer nanoparticles with well-defined surface chemistries were visualized interacting with a growing calcite surface using in situ atomic force microscopy. These nanoparticles comprise a poly(benzyl methacrylate) (PBzMA) core-forming block and a non-ionic poly(glycerol monomethacrylate) (Ph-PGMA), a carboxylic acid-tipped poly(glycerol monomethacrylate) (HOOC-PGMA), or an anionic poly(methacrylic acid) (PMAA) stabilizer block. Our results reveal three modes of interaction between the nanoparticles and the calcite surface: (i) attachment followed by detachment, (ii) sticking to and "hovering" over the surface, allowing steps to pass beneath the immobilized nanoparticle, and (iii) incorporation of the nanoparticle by the growing crystals. By analyzing the relative contributions of these three types of interactions as a function of nanoparticle surface chemistry, we show that ∼85% of PMAA85-PBzMA100 nanoparticles either "hover" or become incorporated, compared to ∼50% of the HOOC-PGMA71-PBzMA100 nanoparticles. To explain this difference, we propose a two-state binding mechanism for the anionic PMAA85-PBzMA100 nanoparticles. The "hovering" nanoparticles possess highly extended polyelectrolytic stabilizer chains and such chains must adopt a more "collapsed" conformation prior to successful nanoparticle occlusion. This study provides a conceptual framework for understanding how sterically stabilized nanoparticles interact with growing crystals, and suggests design principles for improving occlusion efficiencies.

Sodium Bis(acyl)phosphane oxide (SBAPO): An efficient photoinitiator for blue light initiated aqueous RAFT dispersion polymerization

We report a novel blue light initiated aqueous reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) with a poly (glycerol monomethacrylate) homopolymer as the macro-RAFT agent and sodium bis(acyl)phosphane oxide (SBAPO) as the photoinitiator. High monomer conversions were achieved within 1 h of blue light irradiation. Taking advantage of the temperature-insensitive feature of photoinitiator, the effect of reaction temperature on the blue light initiated aqueous RAFT dispersion polymerization was studied in detail. A new morphological phase diagram was constructed for the first time by changing the degree of polymerization (DP) of the core-forming block and the reaction temperature. Moreover, a typical morphological phase diagram for the blue light initiated aqueous RAFT dispersion polymerization at 70 °C was also built and various morphologies have been prepared. Effect of wavelength of light (405 and 465 nm) on copolymer compositions and morphologies was studied. Finally, a fully one-pot blue light initiated aqueous RAFT polymerization was developed for the synthesis of various diblock copolymer nano-objects.

Synthesis of High Molecular Weight Poly(glycerol monomethacrylate) via RAFT Emulsion Polymerization of Isopropylideneglycerol Methacrylate.

High molecular weight water-soluble polymers are widely used as flocculants or thickeners. However, synthesis of such polymers via solution polymerization invariably results in highly viscous fluids, which makes subsequent processing somewhat problematic. Alternatively, such polymers can be prepared as colloidal dispersions; in principle, this is advantageous because the particulate nature of the polymer chains ensures a much lower fluid viscosity. Herein we exemplify the latter approach by reporting the convenient one-pot synthesis of high molecular weight poly(glycerol monomethacrylate) (PGMA) via the reversible addition–fragmentation chain transfer (RAFT) aqueous emulsion polymerization of a water-immiscible protected monomer precursor, isopropylideneglycerol methacrylate (IPGMA) at 70 °C, using a water-soluble poly(glycerol monomethacrylate) (PGMA) chain transfer agent as a steric stabilizer. This formulation produces a low-viscosity aqueous dispersion of PGMA–PIPGMA diblock copolymer nanoparticles at 20% solids. Subsequent acid deprotection of the hydrophobic core-forming PIPGMA block leads to particle dissolution and affords a viscous aqueous solution comprising high molecular weight PGMA homopolymer chains with a relatively narrow molecular weight distribution. Moreover, it is shown that this latex precursor route offers an important advantage compared to the RAFT aqueous solution polymerization of glycerol monomethacrylate since it provides a significantly faster rate of polymerization (and hence higher monomer conversion) under comparable conditions.

Fluorescent Supracolloidal Chains of Patchy Micelles of Diblock Copolymers Functionalized with Fluorophores.

By selective attachment of fluorescent dyes to the core-forming block, we produced patchy micelles of diblock copolymers with fluorophores localized in the micellar cores. From these patchy micelles functionalized with dyes, fluorescent supracolloidal chains in a few micrometers were polymerized by combining the patches in neighboring micelles, indicating that selective modification of the core-forming block delivered the functionality into the supracolloidal chain without altering the polymerization of patchy micelles. Thus, with the same polymerization condition, we were able to produce red-, green-, and blue-emitting supracolloidal chains by varying the fluorescent dyes attached to the core-forming block. In addition, we directly visualized individual supracolloidal chains by fluorescence confocal microscopy as well as by transmission electron microscopy.

Expanding the Scope of Polymerization-Induced Self-Assembly: Z-RAFT-Mediated Photoinitiated Dispersion Polymerization.

In this communication, we developed the first well-controlled Z-RAFT (RAFT = reversible addition-fragmentation chain transfer) mediated polymerization-induced self-assembly (PISA) formulation based on photoinitiated RAFT dispersion polymerization of tert-butyl acrylate (tBA) in ethanol/water (60/40, w/w) at room temperature using a Z-type macromolecular chain transfer agent (macro-CTA). Polymerizations proceeded rapidly via the exposure of visible-light irradiation (405 nm, 0.45 mW/cm2) with high monomer conversion (>95%) being achieved within 1 h. A variety of polymer nano-objects (spheres, worms, and vesicles) with narrow molar mass distributions were prepared by this Z-RAFT mediated PISA formulation. Silver nanoparticles were loaded with the vesicles via in situ reduction, which can be used as a catalyst for the reduction of methylene blue (MB) in the presence of NaBH4. Finally, gel permeation chromatography (GPC) analysis demonstrated that the corona block and the core-forming block could be cleaved by treating with excess initiator. This novel PISA formulation will greatly expand the scope of PISA and provide more mechanistic insights into the PISA research.

Segmental Relaxation Dynamics of the Core and Corona in a Single Dry Micelle

The segmental relaxation dynamics of the core and the corona in a single dry spherical micelle comprising a polystyrene (PS) or poly(methyl methacrylate) (PMMA) core and a poly(acrylic acid) (PAA) corona, along with the effects of the micelle density and the chain length of the core-forming and corona-forming polymers, were investigated by AFM. The results showed that the segmental relaxation temperature in the micelle core was close to its bulk Tg and independent of the micellar structure, such as micelle size, density, and corona thickness. By contrast, the segmental relaxation temperature in the micelle corona is dependent on the micellar structure. The depressed chain mobility in the corona was enhanced as the micelle density and the length of both the corona-forming and core-forming blocks increased. This phenomenon was attributed to conformational entropy loss in the micelle corona because of the chain adopting a conformation more perpendicular to the core as the micelle size and density increased.

Pincushion of Tubule Discovery and Tubular Morphology Landscape Establishment of Block Copolymer Self-Assemblies.

Block copolymer (BCP) self-assembly is a versatile technique in the preparation of polymeric aggregates with varieties of morphologies. However, its morphology library is limited. Here, the discovery of pincushion of tubules is reported for the first time, via BCP self-assembly of poly(4-vinylpyridine)-b-polystyrene (P4VP-b-PS) with very high molecular weight (500 kDa) and asymmetry (2 mol% P4VP). The investigation confirms the importance of core-forming block length on morphology control of BCP self-assemblies, especially with respect to tubular structures. The morphology landscape of tubular structures is successfully established, where dumbbell of tubule, tubule, loose clew of tubules, tight clew of tubules, and pincushion of tubules can be prepared by adjusting the core-forming block length. This work therefore expands the structure library of BCP self-assemblies and opens up a new avenue for the further applications of these tubular materials.

PH-Responsive Schizophrenic Diblock Copolymers Prepared by Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly (PISA) is used for the highly convenient and efficient preparation of ampholytic diblock copolymer nanoparticles directly in acidic aqueous solution. Cationic nanoparticles comprising a protonated polyamine stabilizer block and a hydrophobic polyacid core-forming block are formed at pH 2. Micelle inversion occurs at pH 10 to produce anionic nanoparticles with an ionized polyacid stabilizer block and a hydrophobic polyamine core-forming block. Macroscopic precipitation occurs at around pH 6–7, which lies close to the isoelectric point of this ampholytic diblock copolymer. Incorporation of fluorescein and rhodamine dye labels into the acid and amine blocks, respectively, leads to dual-color bifluorescent self-reporting pH-responsive nanoparticles.

Uniform electroactive fibre-like micelle nanowires for organic electronics

Micelles formed by the self-assembly of block copolymers in selective solvents have attracted widespread attention and have uses in a wide variety of fields, whereas applications based on their electronic properties are virtually unexplored. Herein we describe studies of solution-processable, low-dispersity, electroactive fibre-like micelles of controlled length from π-conjugated diblock copolymers containing a crystalline regioregular poly(3-hexylthiophene) core and a solubilizing, amorphous regiosymmetric poly(3-hexylthiophene) or polystyrene corona. Tunnelling atomic force microscopy measurements demonstrate that the individual fibres exhibit appreciable conductivity. The fibres were subsequently incorporated as the active layer in field-effect transistors. The resulting charge carrier mobility strongly depends on both the degree of polymerization of the core-forming block and the fibre length, and is independent of corona composition. The use of uniform, colloidally stable electroactive fibre-like micelles based on common π-conjugated block copolymers highlights their significant potential to provide fundamental insight into charge carrier processes in devices, and to enable future electronic applications.

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol.

Although siRNA-based nanomedicines hold promise for cancer treatment, conventional siRNA-polymer complex (polyplex) nanocarrier systems have poor pharmacokinetics following intravenous delivery, hindering tumor accumulation. Here, we determined the impact of surface chemistry on the in vivo pharmacokinetics and tumor delivery of siRNA polyplexes. A library of diblock polymers was synthesized, all containing the same pH-responsive, endosomolytic polyplex core-forming block but different corona blocks: 5 kDa (benchmark) and 20 kDa linear polyethylene glycol (PEG), 10 kDa and 20 kDa brush-like poly(oligo ethylene glycol), and 10 kDa and 20 kDa zwitterionic phosphorylcholine-based polymers (PMPC). In vitro, it was found that 20 kDa PEG and 20 kDa PMPC had the highest stability in the presence of salt or heparin and were the most effective at blocking protein adsorption. Following intravenous delivery, 20 kDa PEG and PMPC coronas both extended circulation half-lives 5-fold compared to 5 kDa PEG. However, in mouse orthotopic xenograft tumors, zwitterionic PMPC-based polyplexes showed highest in vivo luciferase silencing (>75% knockdown for 10 days with single IV 1 mg/kg dose) and 3-fold higher average tumor cell uptake than 5 kDa PEG polyplexes (20 kDa PEG polyplexes were only 2-fold higher than 5 kDa PEG). These results show that high molecular weight zwitterionic polyplex coronas significantly enhance siRNA polyplex pharmacokinetics without sacrificing polyplex uptake and bioactivity within tumors when compared to traditional PEG architectures.

Star Architecture Promoting Morphological Transitions during Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly (PISA) via reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization is an effective method to produce block copolymer nano-objects of various morphologies at high solids. However, current PISA formulations have been limited to linear block copolymers. We report the synthesis of AB2 star block copolymers via RAFT aqueous dispersion polymerization of diacetone acrylamide using a poly(ethylene glycol) methyl ether bearing two chain transfer agents as the difunctional macromolecular chain transfer agent (macro-CTA), which was efficiently synthesized using 2,4,6-trichloro-1,3,5-triazine and activated esters to afford a high end functionality (97%). The star polymer architecture can significantly promote morphological transitions to obtain higher-order morphologies at both lower solids and lower degrees of polymerization of the core-forming block in comparison with its linear counterpart. This work demonstrates that polymer architecture is another important parameter that should be considered when conducting PISA synthesis to obtain complex morphologies.

Modular Monomers with Tunable Solubility: Synthesis of Highly Incompatible Block Copolymer Nano-Objects via RAFT Aqueous Dispersion Polymerization.

The high incompatibility of block copolymers consisting of a neutral stabilizer block and a polyelectrolyte core-forming block is exploited to drive phase segregation during polymerization-induced self-assembly (PISA). A modular approach to systematically tune the solubility of ionic monomers/polymers is developed to efficiently identify monomers suitable for aqueous dispersion polymerizations. The strong phase segregation ability of the neutral-polyelectrolyte block copolymers favors the formation of worms over a relatively broad composition range and even at very low solids. These findings suggest that the degree of incompatibility between the stabilizer block and the core-forming block should be considered as one of the key parameters when studying morphological transitions in PISA.

Tadpole and Mixed Linear/Tadpole Micelles of Diblock Copolymers: Thermodynamics and Chain Exchange Kinetics

Chain architecture is known to control macromolecular self-assembly and furthermore affect in a more complex way nanostructure stability. Equilibrium properties and chain exchange kinetics between micelles formed by tadpole-shaped diblock copolymers containing a loop-shaped hydrophobic block and a linear hydrophilic block are investigated using dissipative particle dynamics simulations. We found that tadpoles form micelles of smaller size and aggregation number than the corresponding linear diblock copolymers and have faster chain exchange kinetics, demonstrating that chain architecture can alter its effective hydrophobicity. Similar observations are made for linear diblock copolymer with a less hydrophobic core block indicating that the more compact conformation of tadpole core-forming block makes it “less hydrophobic”. We show that tadpole and linear block copolymers form mixed micelles with tadpoles (or less hydrophobic chains) located on the periphery of the micelle core. The chain exchange kinetics b...

Effect of Monomer Solubility on the Evolution of Copolymer Morphology during Polymerization-Induced Self-Assembly in Aqueous Solution.

Polymerization-induced self-assembly (PISA) has become a widely used technique for the rational design of diblock copolymer nano-objects in concentrated aqueous solution. Depending on the specific PISA formulation, reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization typically provides straightforward access to either spheres, worms, or vesicles. In contrast, RAFT aqueous emulsion polymerization formulations often lead to just kinetically-trapped spheres. This limitation is currently not understood, and only a few empirical exceptions have been reported in the literature. In the present work, the effect of monomer solubility on copolymer morphology is explored for an aqueous PISA formulation. Using 2-hydroxybutyl methacrylate (aqueous solubility = 20 g dm–3 at 70 °C) instead of benzyl methacrylate (0.40 g dm–3 at 70 °C) for the core-forming block allows access to an unusual “monkey nut” copolymer morphology over a relatively narrow range of target degrees of polymerization when using a poly(methacrylic acid) RAFT agent at pH 5. These new anisotropic nanoparticles have been characterized by transmission electron microscopy, dynamic light scattering, aqueous electrophoresis, shear-induced polarized light imaging (SIPLI), and small-angle X-ray scattering.

Adsorption of Small Cationic Nanoparticles onto Large Anionic Particles from Aqueous Solution: A Model System for Understanding Pigment Dispersion and the Problem of Effective Particle Density.

The present study focuses on the use of copolymer nanoparticles as a dispersant for a model pigment (silica). Reversible addition–fragmentation chain transfer (RAFT) alcoholic dispersion polymerization was used to synthesize sterically stabilized diblock copolymer nanoparticles. The steric stabilizer block was poly(2-(dimethylamino)ethyl methacrylate) (PDMA) and the core-forming block was poly(benzyl methacrylate) (PBzMA). The mean degrees of polymerization for the PDMA and PBzMA blocks were 71 and 100, respectively. Transmission electron microscopy (TEM) studies confirmed a near-monodisperse spherical morphology, while dynamic light scattering (DLS) studies indicated an intensity-average diameter of 30 nm. Small-angle X-ray scattering (SAXS) reported a volume-average diameter of 29 ± 0.5 nm and a mean aggregation number of 154. Aqueous electrophoresis measurements confirmed that these PDMA71–PBzMA100 nanoparticles acquired cationic character when transferred from ethanol to water as a result of protonation of the weakly basic PDMA chains. Electrostatic adsorption of these nanoparticles from aqueous solution onto 470 nm silica particles led to either flocculation at submonolayer coverage or steric stabilization at or above monolayer coverage, as judged by DLS. This technique indicated that saturation coverage was achieved on addition of approximately 465 copolymer nanoparticles per silica particle, which corresponds to a fractional surface coverage of around 0.42. These adsorption data were corroborated using thermogravimetry, UV spectroscopy and X-ray photoelectron spectroscopy. TEM studies indicated that the cationic nanoparticles remained intact on the silica surface after electrostatic adsorption, while aqueous electrophoresis confirmed that surface charge reversal occurred below pH 7. The relatively thick layer of adsorbed nanoparticles led to a significant reduction in the effective particle density of the silica particles from 1.99 g cm–3 to approximately 1.74 g cm–3, as judged by disk centrifuge photosedimentometry (DCP). Combining the DCP and SAXS data suggests that essentially no deformation of the PBzMA cores occurs during nanoparticle adsorption onto the silica particles.