The Synthesis of Narrowly Dispersed Poly(ε-caprolactone) Microspheres by Dispersion Polymerization Using a Homopolymer Poly(dodecyl acrylate) as the Stabilizer.

Using dodecyl acrylate as a raw material and 2-Cyanoprop-2-yl-dithiobenzoate as a chain transfer agent, poly(dodecyl acrylate) is synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Using poly(dodecyl acrylate) as stabilizers, narrowly dispersed poly(ε-caprolactone) microspheres with particle sizes ranging from 0.5 to 1.5 µm are successfully synthesized by ring-opening dispersion polymerization. The effects of the molecular weight of poly(dodecyl acrylate), the volume proportion of mixed solvent (i.e., 1,4-dioxane/heptane), and the reaction temperature on the particle size and its distribution are investigated. With careful control of the synthesis condition, microspheres can be obtained with a particle size distribution of 1.09 (Dw/Dn). The average particle size of poly(ε-caprolactone) microspheres decreased with the increase in the molecular weight of poly(dodecyl acrylate) and increased with the increase in the relative content of 1,4-dioxane. The uniformity of microspheres decreased with the increase in the polymerization temperature.

Modern Trends in Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly (PISA) is a powerful and versatile technique for producing colloidal dispersions of block copolymer particles with desired morphologies. Currently, PISA can be carried out in various media, over a wide range of temperatures, and using different mechanisms. This method enables the production of biodegradable objects and particles with various functionalities and stimuli sensitivity. Consequently, PISA offers a broad spectrum of potential commercial applications. The aim of this review is to provide an overview of the current state of rational synthesis of block copolymer particles with diverse morphologies using various PISA techniques and mechanisms. The discussion begins with an examination of the main thermodynamic, kinetic, and structural aspects of block copolymer micellization, followed by an exploration of the key principles of PISA in the formation of gradient and block copolymers. The review also delves into the main mechanisms of PISA implementation and the principles governing particle morphology. Finally, the potential future developments in PISA are considered.

In Situ Fabrication of Silver Nanoparticle-Decorated Polymeric Vesicles for Antibacterial Applications.

Silver/polymeric vesicle composite nanoparticles with good antibacterial properties were fabricated in this study. Silver nanoparticles (AgNPs) were prepared in situ on cross-linked vesicle membranes through the reduction of silver nitrate (AgNO3) using polyvinylpyrrolidone (PVP) via coordination bonding between the Ag+ ions and the nitrogen atoms on the vesicles. X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-vis), and transmission electron microscopy (TEM) analyses confirmed the formation of AgNPs on the vesicles. The antibacterial test demonstrated good antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) for the produced AgNP-decorated vesicles. The minimum inhibitory concentration (MIC) values of the AgNP-decorated vesicles for E. coli and S. aureus were 8.4 and 9.6 µg/mL, respectively. Cell viability analysis on the A549 cells indicated that the toxicity was low when the AgNP concentrations did not exceed the MIC values, and the wound healing test confirmed the good antibacterial properties of the AgNP-decorated vesicles.

Biodegradable Covalently Crosslinked Poly[N-(2-Hydroxypropyl) Methacrylamide] Nanogels: Preparation and Physicochemical Properties.

Recently, suitably sized polymer-based nanogels containing functional groups for the binding of biologically active substances and ultimately degradable to products that can be removed by glomerular filtration have become extensively studied systems in the field of drug delivery. Herein, we designed and tailored the synthesis of hydrophilic and biodegradable poly[N-(2-hydroxypropyl) methacrylamide-co-N,N'-bis(acryloyl) cystamine-co-6-methacrylamidohexanoyl hydrazine] (PHPMA-BAC-BMH) nanogels. The facile and versatile dispersion polymerization enabled the preparation of nanogels with a diameter below 50 nm, which is the key parameter for efficient and selective passive tumor targeting. The effects of the N,N'-bis(acryloyl) cystamine crosslinker, polymerization composition, and medium including H2O/MetCel and H2O/EtCel on the particle size, particle size distribution, morphology, and polymerization kinetics and copolymer composition were investigated in detail. We demonstrated the formation of a 38 nm colloidally stable PHPMA-BAC-BMH nanogel with a core-shell structure that can be rapidly degraded in the presence of 10 mM glutathione solution under physiologic conditions. The nanogels were stable in an aqueous solution modeling the bloodstream; thus, these nanogels have the potential to become highly important carriers in the drug delivery of various molecules.

Determination of Reaction Kinetics by Time-Resolved Small-Angle X-ray Scattering during Polymerization-Induced Self-Assembly: Direct Evidence for Monomer-Swollen Nanoparticles.

The kinetics of heterogeneous polymerization is determined directly using small-angle X-ray scattering (SAXS). This important advancement is exemplified for the synthesis of sterically-stabilized diblock copolymer nanoparticles by reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) in mineral oil at 90 °C. The principle of mass balance is invoked to derive a series of equations for the analysis of the resulting time-resolved SAXS patterns. Importantly, there is a continuous change in the X-ray scattering length density for the various components within the reaction mixture. This enables the volume fraction of unreacted BzMA monomer to be calculated at any given time point, which enables the polymerization kinetics to be monitored in situ directly without relying on supplementary characterization techniques. Moreover, SAXS enables the local concentration of both monomer and solvent within the growing swollen nanoparticles to be determined during the polymerization. Data analysis reveals that the instantaneous rate of BzMA polymerization is proportional to the local monomer concentration within the nanoparticles. In principle, this powerful new time-resolved SAXS approach can be applicable to other heterogeneous polymerization formulations.

Tunable Reflection through Size Polydispersity of Chiral-Nematic Liquid Crystal Polymer Particles.

Micro-sized chiral-nematic liquid crystal (N* LC) polymer particles have attracted considerable interest as versatile reflective colorants with selective circularly polarized light (CPL) properties. However, challenges in achieving the desired size distribution of N* LC particles have led to an incomplete understanding of their reflective characteristics. In this study, we successfully synthesized N* LC particles via dispersion polymerization, enabling precise control over size polydispersity by manipulating the composition of the polymerization solvent. Our investigation revealed that monodisperse N* LC particles displayed distinct reflection bands with high CPL selectivity, while polydisperse particles exhibited broader reflection with lower CPL selectivity. These findings underscore the potential to synthesize N* LC particles with tailored reflective properties using identical monomeric compounds. Furthermore, we demonstrated the production of multifunctional reflective colorants by blending N* LC particles with varying reflection colors. These discoveries hold significant promise for advancing the development of reflective colorants and anti-counterfeiting printing techniques utilizing micro-sized N* LC particles.

Synthesis of dimpled polymer particles and polymer particles with protrusions - Past, present, and future.

Since the development of emulsion polymerization techniques, polymer particles have become the epitome of standard colloids due to the exceptional control over size, size distribution, and composition the synthesis methods allow reaching. The exploration of different variations of the synthesis methods has led to the discovery of more advanced techniques, enabling control over their composition and shape. Many early investigations focused on forming particles with protrusions (with one protrusion, called dumbbell particles) and particles with concavities, also called dimpled particles. This paper reviews the literature covering the synthesis, functionalization, and applications of both types of particles. The focus has been on the rationalization of the various approaches used to prepare such particles and on the discussion of the mechanisms of formation not just from the experimental viewpoint but also from the standpoint of thermodynamics. The primary motivation to combine in a single review the preparation of both types of particles has been the observation of similarities among some of the methods developed to prepare dimpled particles, which sometimes include the formation of particles with protrusions and vice versa. The most common applications of these particles have been discussed as well. By looking at the different approaches developed in the literature under one general perspective, we hope to stimulate a more ample use of these particles and promote the development of even more effective synthetic protocols.

Hydrophobically Associating Polyacrylamide "Water-in-Water" Emulsion Prepared by Aqueous Dispersion Polymerization: Synthesis, Characterization and Rheological Behavior.

The hydrophobically associating polyacrylamide (HAPAM) is an important kind of water-soluble polymer, which is widely used as a rheology modifier in many fields. However, HAPAM products prepared in a traditional method show disadvantages including poor water solubility and the need for hydrocarbon solvents and appropriate surfactants, which lead to environmental pollution and increased costs. To solve these problems, we reported a novel kind of HAPAM "water-in-water" (w/w) emulsion and its solution properties. In this work, a series of cationic hydrophobic monomers with different alkyl chain lengths were synthesized and characterized. Then, HAPAM w/w emulsions were prepared by the aqueous dispersion polymerization of acrylamide, 2-methylacryloylxyethyl trimethyl ammonium chloride and a hydrophobic monomer. All these emulsions can be stored more than 6 months, showing excellent stability. An optical microscopy observation showed that the particle morphology and the particle size of the HAPAM emulsion were more regular and bigger than the emulsion without the hydrophobic monomer. The solubility tests showed that such HAPAM w/w emulsions have excellent solubility, which took no more than 180 s to dilute and achieve a homogeneous and clear solution. The rheology measurements showed that the HAPAM association increases with a hydrophobe concentration or the length of hydrophobic alkyl chains, resulting in better shear and temperature resistances. The total reduced viscosity was 124.42 mPa·s for cw101, 69.81 mPa·s for cw6-1, 55.38 mPa·s for cw8-0.25, 48.95 mPa·s for cw12-0.25 and 28 mPa·s for cw16-0.25 when the temperature increased from 30 °C to 90 °C. The cw8-2.0 that contains a 2 mol% hydrophobe monomer has the lowest value at 19.12 mPa·s due to the best association. Based on the excellent stability, solubility and rheological properties, we believe that these HAPAM w/w emulsions could find widespread applications.

In-depth study of anticancer drug diffusion through a cross-linked -pH-responsive polymeric vesicle membrane.

Post-encapsulation and release of the anticancer drug doxorubicin hydrochloride (DOX·HCl) through cell-like transmission functions of polymeric vesicles were studied using cross-linked pH-responsive polymeric vesicles. The vesicles were fabricated for the first time via the redox-initiated reversible addition-fragmentation chain transfer dispersion polymerization in ethanol-water mixture, using 2-(diisopropylamino)ethyl methacrylate and glycidyl methacrylate, and the vesicle membrane was modified post-cross-linking by using ethylenediamine. A phase diagram was constructed for reproducible fabrication of the polymeric vesicles, and well-shaped vesicles were formed when the target degree of polymerization of the hydrophobic polymer chains was equal to or higher than 50 with solid content in the range of 10-30 wt%. The cross-linked vesicle membrane served as a gate enabling "open" and "closed" states in response to pH stimulation. Up to 50% drug loading efficiency and 39% drug loading content could be achieved, and in vitro release of the DOX-loaded vesicles in aqueous buffer solutions showed a much faster DOX release rate at pH 5.0 than at pH 6.5. The polymeric vesicles were of very low cytotoxicity to A549 cells up to the concentration of 2 mg/mL, and the IC50 of DOX-loaded vesicles were higher than that of the free DOX. The intracellular DOX release study indicated higher cellular uptake capability for DOX-loaded vesicles than that of free DOX.

Dispersion polymerization induced self-assembly (pisa) techniques for the fabrication of polymeric nanoparticles for biomedical applications.

Nanoparticles offer several advantages in drug delivery. The progress in the development of nanoparticles for biomedical applications has moved from the first generation nanoparticles to the fifth generation nanoparticles and the transitions reflect their increasing versatility in biomedical applications. Polymeric nanoparticles are prepared mainly by two methods: dispersion of preformed polymers and in situ polymerization of monomers and macromonomers. Polymerization induced self-assembly (PISA) for the fabrication of nanoparticles is believed to be a better strategy than nanoparticle fabrication from preformed polymers (ease of tethering targeting ligands to the corona of the nanoparticles and unlike PISA, creation of nanostructures via self-assembly of block copolymers is performed in low concentrations. Dispersion polymerization involves one-pot synthesis of nanoparticles. RDRP processes such as atom transfer radical polymerization, reversible addition-fragmentation chain transfer polymerization and nitroxide mediated polymerization have revolutionized polymer synthesis by providing polymer chemists with powerful tools that enable control over architecture, composition and chain length distributions. The technique for the fabrication of nanoparticles by dispersion polymerization (PISA) at ambient temperature was described with examples from our laboratory involving organic redox initiated polymerization using the FDA approved biodegradable polymers. Computer optimization is useful in understanding the factors that ensure optimized properties of drug-loaded nanoparticles.

Design of novel temperature-resistant and salt-tolerant acrylamide-based copolymers by aqueous dispersion polymerization.

Development of polymer-based flooding technology to improve oil recovery efficiency, water dispersion copolymerization of acrylamide, cationic monomer methacryloxyethyltrimethyl ammonium chloride (METAC), and anionic monomer acrylic acid (AA) were carried out in aqueous ammonium sulfate solution with polyvinyl pyrrolidone (PVP) as the stabilizer. The copolymers were characterized by 1H-NMR, FT-IR, TG, and SEM to confirm that they were prepared successfully and exhibited excellent salt-resistant property. Moreover, the effect of the aqueous solution of ammonium sulfate (AS) concentration, stabilizer concentration, and initiator concentration on the viscosity and size were systematically investigated. To further improve the thermal endurance properties of copolymer, hydrophobic monomers with different alkyl chain lengths were added to the above system. The acrylamide-based quadripolymer possessed prominent thermal and salt endurance properties by utilizing the advantages of zwitterionic structure and hydrophobic monomer. With the temperature rising, the viscosity retention could reach 70.2% in the water and 63.8% in the saline. This work had expected to provide a new strategy to design polymers with excellent salinity tolerance and thermal-resistance performances.

Reverse Sequence Polymerization-Induced Self-Assembly in Aqueous Media.

We report a new aqueous polymerization-induced self-assembly (PISA) formulation that enables the hydrophobic block to be prepared first when targeting diblock copolymer nano-objects. This counter-intuitive reverse sequence approach uses an ionic reversible addition-fragmentation chain transfer (RAFT) agent for the RAFT aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) to produce charge-stabilized latex particles. Chain extension using a water-soluble methacrylic, acrylic or acrylamide comonomer then produces sterically stabilized diblock copolymer nanoparticles in an aqueous one-pot formulation. In each case, the monomer diffuses into the PHPMA particles, which act as the locus for the polymerization. A remarkable change in morphology occurs as the ≈600 nm latex is converted into much smaller sterically stabilized diblock copolymer nanoparticles, which exhibit thermoresponsive behavior. Such reverse sequence PISA formulations enable the efficient synthesis of new functional diblock copolymer nanoparticles.

The preparation of novel AIE fluorescent microspheres by dispersion polymerization.

An approach to prepare monodisperse polystyrene microspheres with aggregation-induced emission (AIE) characteristics has been developed which shows promising applications in fluorescence-encoding. The micron-sized, monodisperse polystyrene microspheres with AIE molecules were perfectly synthesized by two-stage dispersion polymerization. Fluorescent AIE monomer was synthesized by Suzuki reaction, confirmed by nuclear magnetic resonance (NMR). These AIE fluorogens (AIEgens) exhibited unique properties such as bright green emission in solid state and increased emission in tetrahydrofuran (THF) solution with the increase of water content. The influence of the AIE molecules concentration to microspheres synthesis was well investigated. The reaction conditions were optimized to obtain the functional polystyrene microspheres with a size distribution around 3%. The novel microspheres were characterized by scanning electron microscopy (SEM), confocal fluorescence microscope and flow cytometry. According to these results, two-stage dispersion polymerization was proved to be an efficient pathway for the preparation of AIE fluorescent and functionalized microspheres, which could be used in many biomedical industries.

Simultaneous Synthesis and Self-Assembly of Bottlebrush Block Copolymers at Room Temperature via Photoinitiated RAFT Dispersion Polymerization.

Bottlebrush polymers exhibiting unique properties have attracted considerable attention for applications in many research areas. Herein, the first simultaneous synthesis and self-assembly of bottlebrush block copolymers at room temperature via photoinitiated polymerization-induced self-assembly (photo-PISA) using multifunctional macromolecular chain transfer agents (macro-CTAs) is reported. Comparing with linear block copolymers, the bottlebrush block copolymers can promote the formation of higher-order morphologies (e.g., vesicles) when targeting similar degrees of polymerization (DPs). Moreover, a higher polymerization rate is observed in the case of bottlebrush block copolymers. Gel permeation chromatography (GPC) analysis shows that good polymerization control is maintained when synthesizing bottlebrush block copolymers by photo-PISA. Finally, the obtained bottlebrush block copolymer vesicles are used as seeds for further chain extension and multicompartment nanoparticles with a sponge internal structure are formed. It is expected that this study will not only expand polymer architectures employed in PISA, but also provide a new strategy to synthesize polymer nanoparticles with unique structures.

Dispersion Polymerization versus Emulsifier-Free Emulsion Polymerization for Nano-Object Fabrication: A Comprehensive Comparison.

Although the preparation of nano-objects by emulsifier-free controlled/living radical emulsion polymerization has drawn much attention, the morphologies of these formed objects are difficult to predict and to reproduce because of the much more complex nucleation mechanisms of emulsion polymerization compared to only one self-assembling nucleation mechanism of controlled radical dispersion polymerization. The present study compares dispersion polymerization with emulsifier-free emulsion polymerization in terms of nucleation mechanism, polymerization kinetics, and disappearance behavior of the macrochain transfer agent, gel permeation chromatograms curves of the obtained block copolymer as well as the structural and morphological differences between the produced nano-objects on the basis of published data. Moreover, the effects of the inherently heterogeneous nature of emulsion polymerization on the mechanism of reversible addition-fragmentation transfer polymerization and the nano-object morphology are examined, and efficient agitation and adequate solubility of the core-forming monomer in water are identified as the most crucial factors for the fabrication of nonspherical nano-objects.

Production of NiMn2O4 hollow spheres and CoFe2O4 bowl-like structures by using block copolymer stabilized polystyrene spheres as a hard template.

The aim of this study is to highlight the use of polystyrene (PS) latexes stabilized with block copolymers as a hard template in the production of metal oxide hollow spheres. PS latexes produced by dispersion polymerization by stabilizing with tertiary amine methacrylate-based diblock copolymer were used as a hard template in the preparation of nickel manganese oxide (NiMn2O4) hollow spheres and cobalt iron oxide (CoFe2O4) bowl-like structures. Thanks to the diblock copolymer stabilizer with tertiary amine functional groups on the PS surface, precursor salts of CoFe2O4 and NiMn2O4 were first homogeneously deposited on the surface of PS latexes with a controlled precipitation technique. Then, metal oxide hollow spheres and bowl-like structures were produced by calcination. XRD results showed that CoFe2O4 and NiMn2O4 structures were successfully obtained after calcination. The thermogravimetric analysis results showed that the CoFe2O4 and NiMn2O4 contents of the hybrid PS spheres were in the range of 26.0-28.6 wt%. SEM images showed that the inorganic-polymer spheres fused with each other after calcination to form larger magnetic CoFe2O4 bowl-like structures. SEM images also indicated successful production of highly rough NiMn2O4 hollow spheres with nanosheets on the surface.

Synthesis and Electronic Applications of Particle-Templated Ti3C2Tz MXene-Polymer Films via Pickering Emulsion Polymerization.

MXene/polymer composites have gained widespread attention due to their high electrical conductivity and extensive applications, including electromagnetic interference (EMI) shielding, energy storage, and catalysis. However, due to the difficulty of dispersing MXenes in common polymers, the fabrication of MXene/polymer composites with high electrical conductivity and satisfactory EMI shielding properties is challenging, especially at low MXene loadings. Here, we report the fabrication of MXene-armored polymer particles using dispersion polymerization in Pickering emulsions and demonstrate that these composite powders can be used as feedstocks for MXene/polymer composite films with excellent EMI shielding performance. Ti3C2Tz nanosheets are used as the representative MXene, and three different monomers are used to prepare the armored particles. The presence of nanosheets on the particle surface was confirmed by X-ray photoelectron spectroscopy and scanning electron microscopy. Hot pressing the armored particles above Tg of the polymer produced Ti3C2Tz/polymer composite films; the films are electrically conductive because of the network of nanosheets templated by the particle feedstocks. For example, the particle-templated Ti3C2Tz/polystyrene film had an electrical conductivity of 0.011 S/cm with 1.2 wt % of Ti3C2Tz, which resulted in a high radio frequency heating rate of 13-15 °C/s in the range of 135-150 MHz and an EMI shielding effectiveness of ∼21 dB within the X band. This work provides a new approach to fabricate MXene/polymer composite films with a templated electrical network at low MXene loadings.

Tuneable Time Delay in the Burst Release from Oxidation-Sensitive Polymersomes Made by PISA.

Reactive polymersomes represent a versatile artificial cargo carrier system that can facilitate an immediate release in response to a specific stimulus. The herein presented oxidation-sensitive polymersomes feature a time-delayed release mechanism in an oxidative environment, which can be precisely adjusted by either tuning the membrane thickness or partial pre-oxidation. These polymeric vesicles are conveniently prepared by PISA allowing the straightforward and effective in situ encapsulation of cargo molecules, as shown for dyes and enzymes. Kinetic studies revealed a critical degree of oxidation causing the destabilization of the membrane, while no release of the cargo is observed beforehand. The encapsulation of glucose oxidase directly transforms these polymersomes into glucose-sensitive vesicles, as small molecules including sugars can passively penetrate their membrane. Considering the ease of preparation, these polymersomes represent a versatile platform for the confinement and burst release of cargo molecules after a precisely adjustable time span in the presence of specific triggers, such as H2 O2 or glucose.

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.

Semi-Fluorinated Di and Triblock Copolymer Nano-Objects Prepared via RAFT Alcoholic Dispersion Polymerization (PISA).

A set of well-defined amphiphilic, semi-fluorinated di and triblock copolymers were synthesized via polymerization-induced self-assembly (PISA) under alcoholic dispersion polymerization conditions. This study investigates the influence of the length, nature and position of the solvophobic semi-fluorinated block. A poly(N,N-dimethylaminoethyl methacrylate) was used as the stabilizing block to prepare the di and tri block copolymer nano-objects via reversible addition-fragmentation chain transfer (RAFT) controlled dispersion polymerization at 70 °C in ethanol. Benzylmethacrylate (BzMA) and semi-fluorinated methacrylates and acrylates with 7 (heptafluorobutyl methacrylate (HFBMA)), 13 (heneicosafluorododecyl methacrylate (HCFDDMA)) and 21 (tridecafluorooctyl acrylate (TDFOA)) fluorine atoms were used as monomers for the core-forming blocks. The RAFT polymerization of these semi-fluorinated monomers was monitored by SEC and 1H NMR. The evolution of the self-assembled morphologies was investigated by transmission electron microscopy (TEM). The results demonstrate that the order of the blocks and the number of fluorine atoms influence the microphase segregation of the core-forming blocks and the final morphology of the nano-objects.