Polymerization-induced Self-assembly Research Articles

Aldehyde-Functional Diblock Copolymer Nano-objects via RAFT Aqueous Dispersion Polymerization.

We report the rational design of aldehyde-functional sterically stabilized diblock copolymer nano-objects in aqueous solution via polymerization-induced self-assembly. More specifically, reversible addition-fragmentation chain transfer aqueous dispersion polymerization of 2-hydroxypropyl methacrylate is conducted using a water-soluble precursor block in which every methacrylic repeat unit contains a pendent oligo(ethylene glycol) side chain capped with a cis-diol unit. Systematic variation of the reaction conditions enables the construction of a pseudo-phase diagram, which ensures the reproducible targeting of pure spheres, worms, or vesicles. Selective oxidation of the pendent cis-diol groups using aqueous sodium periodate under mild conditions introduces geminal diols (i.e., the hydrated form of an aldehyde obtained in the presence of water) into the steric stabilizer chains without loss of colloidal stability. In the case of diblock copolymer vesicles, such derivatization leads to the formation of a worm population, indicating partial loss of the original morphology. However, this problem can be circumvented by cross-linking the membrane-forming block prior to periodate oxidation. Moreover, such covalently stabilized aldehyde-functionalized vesicles can be subsequently reacted with either glycine or histidine in aqueous solution, followed by reductive amination to prevent hydrolysis of the labile imine bond. ζ potential measurements confirm that this derivatization significantly affects the electrophoretic behavior of these vesicles. Similarly, the membrane-crosslinked aldehyde-functionalized vesicles can be reacted with a model globular protein, bovine serum albumin, to produce "stealthy" protein-decorated vesicles.

Morphological Control of Nanoparticles via Precision Polymerization-Induced Self-Assembly

Morphological Control of Nanoparticles via Precision Polymerization-Induced Self-Assembly

Polymerization-Induced Self-Assembly of Tea Polyphenols into Open-Mouthed Nanoparticles for Active Delivery Systems and Stable Carbon Bowls

Polyphenol-based hollow nanoparticles have exhibited intriguing properties in drug delivery, catalysis, and energy storage, and the open-mouthed (bowl-shaped) structure is supposed to improve the performance of the nanoparticles by increasing the accessibility of the inner surface and the cavity. Up to now, cationic polymers, metal ions, and sacrificial templates are generally applied in the preparation of the polyphenol-based hollow nanoparticle, and these polyphenols are usually confined to tannin acid and lignin. Seeking for the novel assembly strategy with a wide selection of polyphenolic compounds would open a new horizon for the design, preparation, and applications of polyphenol-based functional materials. In this study, polyphenol nanoparticles with bowl-shaped structure were efficiently prepared through the polymerization-induced self-assembly of tea polyphenols in a few minutes. The formation mechanism was proposed on the basis of a series of TEM images revealing the morphology evolution process. The nanoparticles with good stability in carbonization process are candidates for bowl-shaped carbon spheres. These nanoparticles exhibit potent radical scavenging capacity, anticancer activity, high adsorption capacity of guest molecules (DOX and methylene blue), and pH-dependent release property, with promising use as active delivery systems. Moreover, the present polyphenol assembly strategy provides inspiration for fundamental studies on structure–property–function relationship of polyphenol-based materials.

Synthesis of Biologically Decomposable Terpolymer Nanocapsules and Higher‐Order Nanoassemblies Using RCMP‐PISA

AbstractTerpolymers are used to generate bio‐decomposable self‐assemblies. PEG‐PVL‐PGMA terpolymers are synthesized via a combination of organocatalyzed living radical polymerization (RCMP) with polymerization‐induced self‐assembly (PISA), generating vesicle, multicompartment micelle (MCM), and core‐compartmentalized worm (CCW), where PEG, PVL, and PGMA are poly(ethylene glycol) monomethyl ether, poly(δ‐valerolactone), and poly(glycidyl methacrylate) and PGMA is grown during the PISA. MCM and CCW are uniquely obtainable using terpolymers. The PVL segment is biodegradable, and the obtained assemblies are bio‐decomposable. Heavy metal‐free and sulfur‐free synthesis and bio‐decomposability of the assemblies are attractive features.

Effect of Solvophilic Chain Length in PISA Particles on Pickering Emulsion†

Main observation and conclusionThe morphology of polymeric nanoparticles prepared by polymerization‐induced self‐assembly (PISA) is depended on the degree of polymerization of the solvophilic and solvophobic blocks. Herein, a series of poly (N,N‐dimethylaminoethyl methacrylate)‐b‐poly (benzyl methacrylate) (PDMA‐b‐PBzMA) diblock copolymer spherical nanoparticles were synthesized via reversible addition‐fragmentation chain transfer (RAFT) mediated PISA. These diblock copolymer nanoparticles are with nearly the same hydrodynamic size and solvophobic chain length, but with different solvophilic chain length. We used these nanoparticles to stabilize the oil‐in‐water Pickering emulsion. We find that the stability of Pickering emulsion increases with the length of solvophilic chain of the nanoparticles. Moreover, the droplet size of the Pickering emulsion can be tailored by varying the oil/water ratio and concentration of nanoparticles.

One-Pot Synthesis of Oxidation-Sensitive Supramolecular Gels and Vesicles.

Polypeptide-based nanoparticles offer unique advantages from a nanomedicine perspective such as biocompatibility, biodegradability, and stimuli-responsive properties to (patho)physiological conditions. Conventionally, self-assembled polypeptide nanostructures are prepared by first synthesizing their constituent amphiphilic polypeptides followed by postpolymerization self-assembly. Herein, we describe the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles. This was achieved by polymerization-induced self-assembly (PISA) of the N-carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). By adjusting the hydrophobic block length and concentration, we obtained a range of morphologies from spherical to wormlike micelles, to vesicles. Remarkably, the secondary structure of polypeptides greatly influenced the final morphology of the assemblies. Surprisingly, wormlike micellar morphologies were obtained for a wide range of methionine block lengths and solid contents, with spherical micelles restricted to very short hydrophobic lengths. Wormlike micelles further assembled into oxidation-sensitive, self-standing gels in the reaction pot. Both vesicles and wormlike micelles obtained using this method demonstrated to degrade under controlled oxidant conditions, which would expand their biomedical applications such as in sustained drug release or as cellular scaffolds in tissue engineering.

Reversible CO2-, Photo- and Thermo- Triple Responsive Supramolecular Chirality of Azo-containing Block Copolymer Assemblies Prepared by Polymerization-induced Chiral Self-assembly

Reversible CO2-, Photo- and Thermo- Triple Responsive Supramolecular Chirality of Azo-containing Block Copolymer Assemblies Prepared by Polymerization-induced Chiral Self-assembly

How a family of nanostructured amphiphilic block copolymers synthesized by RAFT-PISA take advantage of thiol groups to direct the in situ assembly of high luminescent CuNCs within their thermo-responsive core

• Multithiolated block copolymer nanoparticles (P-NPs) were synthesized by RAFT-PISA. • Monodisperse P-NPs with tunable size are formed under uncontrolled RAFT polymerization. • P-NPs with thermo-responsive core and hydrophilic shell exhibit high water stability. • Thiolated P-NPs serve as template for in situ assembly of luminescent CuNCs in water. • Fluorescent nanohybrids exhibit pH/thermo-response, photostability and oxidation resistance. The development of fluorescent water stable copper nanoclusters (CuNCs) deserves the scientific interest due to their outstanding properties and low-cost. These fluorescent CuNCs can be synthesized using natural or synthetic polymers with thiol groups. Herein, for the first time, we propose the use of novel amphiphilic block copolymer nano-objects, synthesized by polymerization induced self-assembly (PISA) via reversible-addition fragmentation chain transfer (RAFT), as templates for the synthesis and water stabilization of CuNCs. The polymeric NPs provide water-stability due to the poly(hydroxyethyl acrylate) corona and the thermos-responsive core, based on 2-(2-methoxyethoxy) ethyl methacrylate (MEO 2 MA) and 2-(acetylthio) ethyl methacrylate (AcSEMA) decorated with protected thiol groups, drive the “ in situ ” reduction of copper ions into copper nanocrystals and their assembling in high luminescent nanohybrids in water. In order to optimize the fluorescence properties a methodical study was carried out varying polymers composition and architecture, thiol content and nanoparticle size. All the polymeric nanoparticles synthesized by PISA and decorated with thiol groups induce the formation of luminescent CuNCs in their hydrophobic core. The sizes of the hydrophilic/hydrophobic block, as well as, thiol content are key factors in the emission properties of the CuNC nanohybrids that offer high colloidal stability in water, pH- and thermo-response, significance photostability and strong resistance to oxidation.

Synthesis of Poly(methacrylic acid)-block-Polystyrene Diblock Copolymers at High Solid Contents via RAFT Emulsion Polymerization.

The combination of polymerization–induced self-assembly (PISA) and reversible–addition fragmentation chain transfer (RAFT) emulsion polymerization offers a powerful technique to synthesize diblock copolymers and polymeric nanoparticles in a controlled manner. The RAFT emulsion diblock copolymerization of styrene and methacrylic acid (MAA) by using a trithiocarbonate as surfactant and RAFT agent was investigated. The Z-group of the RAFT agent was modified with a propyl-, butyl- and dodecyl- sidechain, increasing the hydrophobicity of the RAFT agent to offer well-controlled polymerization of poly(methacrylic acid)-block-polystyrene (PMAA-b-PS) diblock copolymers at high solid contents between 30–50 wt% in water. The kinetic data of the PMAA homopolymerization with the three different RAFT agents for various solvents was investigated as well as the RAFT emulsion polymerization of the diblock copolymers in pure water. While the polymerization of PMAA-b-PS with a propyl terminus as a Z-group suffered from slow polymerization rates at solid contents above 30 wt%, the polymerization with a dodecyl sidechain as a Z-group led to full conversion within 2 h, narrow molar mass distributions and all that at a remarkable solid content of up to 50 wt%.

Liquid-Phase Condensation via Macromolecular Crowding in Polymerization-Induced Electrostatic Self-Assembly.

Macromolecular crowding plays a key role in liquid-phase condensation of proteins and membraneless organelles yet is largely unexplored for artificial liquid materials. Herein, we present a strategy for direct access to multiphase liquid condensates with individual charged/neutral subdomains, by introducing macromolecular crowding to our previous protocol of liquid-liquid phase-separation-driven polymerization-induced electrostatic self-assembly (LLPS-PIESA). We show that reversible addition fragmentation chain transfer (RAFT) aqueous dispersion photo-copolymerization of a charged monomer with a specific neutral monomer, in the presence of a polar macrochain transfer agent (CTA) and an oppositely charged polyion, can induce self-sorting and macromolecular crowding. LLPS-PIESA proceeds via liquid-phase condensation of as-assembled nascent clusters up to biologically important nanostructured multiphase condensates with individual charged/neutral subdomains.

RAFT Dispersion Polymerization of Methyl Methacrylate in Mineral Oil: High Glass Transition Temperature of the Core-Forming Block Constrains the Evolution of Copolymer Morphology

RAFT dispersion polymerization of a prototypical methacrylic monomer, methyl methacrylate (MMA), is performed in mineral oil using various poly(lauryl methacrylate) (PLMA) precursors prepared with a trithiocarbonate-based RAFT agent. GPC analysis indicated reasonably narrow molecular weight distributions (Mw/Mn ≤ 1.39) for all diblock copolymers, with 1H NMR studies indicating high MMA conversions (≥95%) for all syntheses. An efficient one-pot synthesis protocol enabled high blocking efficiencies to be achieved when targeting higher PMMA DPs. However, the relatively high glass transition temperature (Tg) of the corresponding core-forming PMMA block unexpectedly constrains the evolution in copolymer morphology during polymerization-induced self-assembly (PISA). More specifically, well-defined PLMA22–PMMAx spheres (x = 19–39) and relatively short worms (x = 69–97) can be obtained at 90 °C when using a PLMA22 precursor but targeting higher x values (x ≥ 108) invariably leads to colloidally unstable aggregates of spheres, rather than long worms or vesicles. Interestingly, similar constraints were observed when targeting higher solids, when using n-dodecane instead of mineral oil, or when employing an alternative steric stabilizer block. Raising the PISA synthesis temperature from 90 to 115 °C (i.e., from below to above the Tg of the final PMMA block) does not alleviate this unexpected problem. Moreover, only spherical nanoparticles can be obtained at 115 °C when targeting PMMA DPs between 50 and 400 with the same PLMA22 precursor. This suggests that nanoparticle formation may occur by a chain expulsion/insertion mechanism at this relatively high reaction temperature. PLMA22–PMMAx nanoparticles were characterized in terms of their particle size and morphology using dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). DLS and TEM studies of a 0.1% w/w dispersion of PLMA22–PMMA69 short worms indicated an irreversible worm-to-sphere transition on heating from 20 to 150 °C. Oscillatory rheology and TEM studies indicated that this thermal transition was only partially reversible for a 20% w/w dispersion of PLMA22–PMMA69 short worms.

High-Yield Synthesis of Molecular Bottlebrushes via PISA-Assisted Grafting-from Strategy.

To prepare molecular bottlebrushes with high yield via a grafting-from strategy using a reversible deactivation radical polymerization (RDRP) technique has always been a big challenge due to the intra- and intermolecular radical-radical coupling. Herein, a polymerization-induced self-assembly (PISA)-assisted grafting-from strategy based on reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization was developed to synthesize the Janus molecular bottlebrushes with a well-defined structure and high yield using polynorbornene-g-(poly(ethylene glycols)-branch-RAFT agent) (PNB-g-(PEG-branch-CTA)) as a solvophilic multifunctional macro-CTA. The results indicated the biradical coupling terminations of propagating side chains could be significantly suppressed due to the nanoconfinement effect in the PISA of the generated Janus molecular bottlebrushes. Janus molecular bottlebrushes with a narrow molecular weight distribution (Mw/Mn < 1.25) and negligible intermolecular cross-linking at monomer conversion as high as 84% were prepared, demonstrating the efficiency and versatility of the PISA-assisted grafting-from approach.

Biphenyl-Induced Superhelix in l -Phenylalanine-Based Supramolecular Self-Assembly with Dynamic Morphology Transitions

Biphenyl-Induced Superhelix in <scp>l</scp> -Phenylalanine-Based Supramolecular Self-Assembly with Dynamic Morphology Transitions

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands.

Herein, the postfunctionalization of different non-fouling PISA particles, prepared from either poly(oligo ethylene glycol methyl ether methacrylate) (pPEGMA) and the anticancer drug PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsenonous acid) or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and PENAO were reported. Both PISA particles were reacted with triphenylphosphonium (TPP) as mitochondria targeting units in order to evaluate the changes in cellular uptake or the toxicity of the conjugated arsenic drug. Attachment of TPP onto the PISA particles however was found not to enhance the mitochondrial accumulation, but it did influence overall the biological activity of pMPC-based particles in 2D and 3D cultured sarcoma SW982 cells. When TPP was conjugated to the pMPC PISA particles more cellular uptake as well as better spheroid penetration were observed, while TPP on PEG-based PISA had only little effect. It was hypothesized that TPP on the micelle surface may not be accessible enough to allow mitochondria targeting, but more structural investigations are required to elucidate this.

Expanding the Scope of Polymerization‐Induced Self‐Assembly: Recent Advances and New Horizons

Over the past decade or so, polymerization-induced self-assembly (PISA) has become a versatile method for rational preparation of concentrated block copolymer nanoparticles with a diverse set of morphologies. Much of the PISA literature has focused on the preparation of well-defined linear block copolymers by using linear macromolecular chain transfer agents (macro-CTAs) with high chain transfer constants. In this review, a recent process is highlighted from an unusual angle that has expanded the scope of PISA including i) synthesis of block copolymers with nonlinear architectures (e.g., star block copolymer, branched block copolymer) by PISA, ii) in situ synthesis of blends of polymers by PISA, and iii) utilization of macro-CTAs with low chain transfer constants in PISA. By highlighting these important examples, new insights into the research of PISA and future impact these methods will have on polymer and colloid synthesis are provided.

Precise Synthesis of π-Conjugated Block Copolymers and Polymerization-Induced Chiral Self-Assembly toward Helical Nanofibers with Circularly Polarized Luminescence.

Precise synthesis and efficient self-assembly of semiconducting polymers are of great interest. Herein, we report the controlled synthesis of π-conjugated poly(phenyl isocyanide)-b-poly(phenyleneethylene) (PPI-b-PPE) copolymers via chain extension of ethynyl 4-iodobenzene initiated by Pd(II)-terminated helical poly(phenyl isocyanide) (PPI). The in-situ-generated block copolymers self-assembled into various supramolecular architectures depending on the PPE length. The helical PPI segment induced the block copolymers with an appropriate PPE length self-assemble into helical nanofibers with a controlled size and defined helicity. Interestingly, the chiral assemblies of the block copolymers exhibit intense optical activity and emit clear circularly polarized luminescence.

Chemoadaptive Polymeric Assemblies by Integrated Chemical Feedback in Self-Assembled Synthetic Protocells.

The design and chemical synthesis of artificial material objects which can mimic the functions of living cells is an important ongoing scientific endeavor. A key challenge necessary for fulfilling the criteria for a system to be living currently regards evolution, which is derived from adaptivity. Integrated chemical loops capable of feedback control are required to achieve chemical systems which exhibit adaptivity. To explore this, we present an integrated, two-component orthogonal chemical process involving reversible addition–fragmentation chain transfer (RAFT) based polymerization-induced self-assembly (PISA) and a copper-catalyzed azide–alkyne click (CuAAC) coupling reaction. The chemical processes are linked through electron transfer from the activated chain-transfer agent (CTA) to the dormant Cu(II) precatalyst. We show that combining these complementary chemistries in a single reaction pot resulted in two primary outcomes: (i) simplification of the PISA process to synthesize the macro-CTA in situ from available nonamphiphilic components and (ii) routes to complexity and adaptation involving population dynamics, morphologies, and dissipative phenomena observed during in situ microscopy analysis.

Polymerization-Induced Self-Assembly of Comb-like Amphiphilic Copolymers into Onion-like Vesicles

Polymerization-Induced Self-Assembly of Comb-like Amphiphilic Copolymers into Onion-like Vesicles

Polymerization-Induced Hierarchical Self-Assembly: From Monomer to Complex Colloidal Molecules and Beyond.

The nanoscale hierarchical design that draws inspiration from nature's biomaterials allows the enhancement of material performance and enables multifarious applications. Self-assembly of block copolymers represents one of these artificial techniques that provide an elegant bottom-up strategy for the synthesis of soft colloidal hierarchies. Fast-growing polymerization-induced self-assembly (PISA) renders a one-step process for the polymer synthesis and in situ self-assembly at high concentrations. Nevertheless, it is exceedingly challenging for the fabrication of hierarchical colloids via aqueous PISA, simply because most monomers produce kinetically trapped spheres except for a few PISA-suitable monomers. We demonstrate here a sequential one-pot synthesis of hierarchically self-assembled polymer colloids with diverse morphologies via aqueous PISA that overcomes the limitation. Complex formation of water-immiscible monomers with cyclodextrin via "host-guest" inclusion, followed by sequential aqueous polymerization, provides a linear triblock terpolymer that can in situ self-assemble into hierarchical nanostructures. To access polymer colloids with different morphologies, three types of linear triblock terpolymers were synthesized through this methodology, which allows the preparation of AXn-type colloidal molecules (CMs), core-shell-corona micelles, and raspberry-like nanoparticles. Furthermore, the phase separations between polymer blocks in nanostructures were revealed by transmission electron microscopy and atomic force microscopy-infrared spectroscopy. The proposed mechanism explained how the interfacial tensions and glass transition temperatures of the core-forming blocks affect the morphologies. Overall, this study provides a scalable method of the production of CMs and other hierarchical structures. It can be applied to different block copolymer formulations to enrich the complexity of morphology and enable diverse functions of nano-objects.

In situ cross-linking in RAFT-mediated emulsion polymerization: Reshaping the preparation of cross-linked block copolymer nano-objects by polymerization-induced self-assembly

Large-scale preparation of cross-linked block copolymer nano-objects using polymerization-induced self-assembly (PISA) generally suffers from the limitation that high degrees of cross-linking in the early stage must be avoided. Herein, we demonstrate that the intrinsic monomer-feeding mechanism of reversible addition-fragmentation chain transfer (RAFT)-mediated emulsion polymerization can be used to delay in situ cross-linking during PISA, allowing the preparation of cross-linked block copolymer nano-objects with high cross-linker contents. When using hydrophobic cross-linkers, the cross-linker along with monomer diffuses from monomer droplets to micelles gradually. When using hydrophilic cross-linkers, the cross-linker is prone to stay in water rather than diffuse into hydrophobic micellar cores. 1H NMR analysis confirmed the consumption behavior of cross-linkers during RAFT-mediated emulsion polymerization regardless of cross-linkers used. A variety of cross-linkers with different aqueous solubilities, symmetries, and functional groups were employed to prepare cross-linked block copolymer nano-objects. It is demonstrated that increasing the content of cross-linker promoted the formation of higher-order morphologies. We expect this study will not only expand the scope of RAFT-mediated PISA for in situ preparation of cross-linked block copolymer nano-objects, but also inspires researchers in this field to prepare novel polymer nanoparticles based on the unique mechanism of RAFT-mediated emulsion polymerization.