Seeded RAFT Polymerization-Induced Self-assembly: Recent Advances and Future Opportunities.

Over the past decade, polymerization-induced self-assembly (PISA) has fully proved its versatility for scale-up production of block copolymer nanoparticles with tunable sizes and morphologies; yet, there are still some limitations. Recently, seeded PISA approaches combing PISA with heterogeneous seeded polymerizations have been greatly explored and are expected to overcome the limitations of traditional PISA. In this review, recent advances in seeded PISA that have expanded new horizons for PISA are highlighted including i) general considerations for seeded PISA (e.g., kinetics, the preparation of seeds, the selection of monomers), ii) morphological evolution induced by seeded PISA (e.g., from corona-shell-core nanoparticles to vesicles, vesicles-to-toroid, disassembly of vesicles into nanospheres), and iii) various well-defined nanoparticles with hierarchical and sophisticated morphologies (e.g., multicompartment micelles, porous vesicles, framboidal vesicles, AXn -type colloidal molecules). Finally, new insights into seeded PISA and future perspectives are proposed.

Biomimetic Design of a Robustly Stabilized Folded State Enabling Seed-Initiated Supramolecular Polymerization under Microfluidic Mixing.

We have investigated the folding and assembly behavior of a cystine-based dimeric diamide bearing pyrene units and solubilizing alkyl chains. In low-polarity solvents, it forms a 14-membered ring through double intramolecular hydrogen bonds between two diamide units. The spectroscopic studies revealed that the folded state is thermodynamically unstable and eventually transforms into more energetically stable helical supramolecular polymers that show an enhanced chiral excitonic coupling between the transition dipoles of the pyrene units. Importantly, compared to an alanine-based monomeric diamide, the dimeric diamide exhibits a superior kinetic stability in the metastable folded state, as well as an increased thermodynamic stability in the aggregated state. Accordingly, the initiation of supramolecular polymerization can be regulated using a seeding method even under microfluidic mixing conditions. Furthermore, taking advantage of a self-sorting behavior observed in a mixture of l-cysteine- and d-cysteine-based dimeric diamides, a two-step supramolecular polymerization was achieved by stepwise addition of the corresponding seeds.

Regioselective Seeded Polymerization in Block Copolymer Nanoparticles: Post-Assembly Control of Colloidal Features.

Post-assembly modifications are efficient tools to adjust colloidal features of block copolymer (BCP) particles. However, existing methods often address particle shape, morphology, and chemical functionality individually. For simultaneous control, we transferred the concept of seeded polymerization to phase separated BCP particles. Key to our approach is the regioselective polymerization of (functional) monomers inside specific BCP domains. This was demonstrated in striped PS-b-P2VP ellipsoids. Here, polymerization of styrene preferably occurs in PS domains and increases PS lamellar thickness up to 5-fold. The resulting asymmetric lamellar morphology also changes the particle shape, i.e., increases the aspect ratio. Using 4-vinylbenzyl azide as co-monomer, azides as chemical functionalities can be added selectively to the PS domains. Overall, our simple and versatile method gives access to various multifunctional BCP colloids from a single batch of pre-formed particles.

Constructing Cylindrical Nanostructures Via Directional Morphology Evolution Induced by Seeded Polymerization.

Herein, spindle-shaped block copolymer (BCP) nanoparticles are used in seeded polymerization of methyl methacrylate as a novel approach to generating cylindrical nanostructures. The chain-extension of BCP seeds by an amorphous coil-type polymer within the seed core composed of semifluorinated liquid-crystalline blocks triggers the deforming, stretching, and directional growth of the seeds along the long axis, eventually leads to nanorods.

Seeded Polymerization of an Amide-Functionalized Diketopyrrolopyrrole Dye in Aqueous Media.

The self-assembly of an amide-functionalized dithienyldiketopyrrolopyrrole (DPP) dye in aqueous media was achieved through seed-initiated supramolecular polymerization. Temperature- and time-dependent studies showed that the spontaneous polymerization of the DPP derivative was temporally delayed upon cooling the monomer solution in a methanol/water mixture. Theoretical calculations revealed that an amide-functionalized DPP derivative adopts an energetically favorable folded conformation in the presence of water molecules due to hydration. This conformational change is most likely responsible for the trapping of monomers in the initial stage of the cooperative supramolecular polymerization in aqueous media. However, the monomeric species can selectively interact with externally added fragmented aggregates as seeds through concerted π-stacking and hydrogen-bonding interactions. Consequently, the time course of the supramolecular polymerization and the morphology of the aggregated state can be controlled, and one-dimensional fibers that exhibit a J-aggregate-like bathochromically shifted absorption band can be obtained.

Seeded Polymerization through the Interplay of Folding and Aggregation of an Amino-Acid-based Diamide.

Amino acid based diamides are widely used as a substructure in supramolecular polymers and are also key components of polypeptides that help to understand protein folding. The interplay of folding and aggregation of a diamide was used to achieve seed-initiated supramolecular polymerization. For that purpose, a pyrene-substituted diamide was synthesized in which pyrene is used as a tracer to monitor the supramolecular polymerization. Thermodynamics and time-dependent studies revealed that the folding of the diamide moiety, via the formation of intramolecular hydrogen bonds, effectively prevents a spontaneous nucleation that leads to supramolecular polymerization. Under such out-of-equilibrium conditions, the addition of seeds successfully initiates the supramolecular polymerization. These results demonstrate the utility of such amino acid based diamides in programmable supramolecular polymerizations.

Preparation of porous sulfonated poly(styrene-divinylbenzene) microspheres and its application in hydrophilic and chiral separation.

Monodisperse cross-linked poly (styrene-divinylbenzene) (P(S-DVB)) porous microspheres with a particle size of about 10 µm were obtained by using the improved two-step seed swelling polymerization method. The influence of different crosslinking degree on specific surface area of porous microparticles was carefully investigated. The surface morphology and pore structure of seed microspheres and porous microspheres were characterized by scanning electron microscopy (SEM), accelerated surface area and porosimetry analyzer. Porous P(S-DVB) microparticles were sulfonated and used as a hydrophilic column packing material for high performance liquid chromatography (HPLC). The separation of oxalic acid, formic acid, acetic acid and acrylic acid was achieved by using the sulfonated-P(S-DVB) particles as packing materials in HPLC. The back pressure of sulfonated-P(S-DVB) column could be maintained at especially low level even at high flow rates due to the excellent permeability of the fillers. Moreover, the separation of chiral drugs was successfully carried out by using the chitosan coated sulfonated-P(S-DVB) microspheres as a column packing material in HPLC. By using water soluble non-toxic photosensitive diazoresin (DR) as linker, a green and facile way to modify packing materials was developed.

Current status and future developments in preparation and application of nonspherical polymer particles.

Nonspherical polymer particles (NPPs) are nano/micro-particulates of macromolecules that are anisotropic in shape, and can be designed anisotropic in chemistry. Due to shape and surface anisotropies, NPPs bear many unique structures and fascinating properties which are distinctly different from those of spherical polymer particles (SPPs). In recent years, the research on NPPs has surprisingly blossomed in recent years, and many practical materials based on NPPs with potential applications in photonic device, material science and biomedical engineering have been generated. In this review, we give a systematic, balanced and comprehensive summary of the main aspects of NPPs related to their preparation and application, and propose perspectives for the future developments of NPPs.

Fabrication of shape-tunable macroparticles by seeded polymerization of styrene using non-cross-linked starch-based seed.

Nonspherical colloidal particles with various geometries and different compositions have attracted tremendous attention and been widely researched. The preparation of polymer colloidal particles with controlled shapes by seeded polymerization is recognized as the most promising technique owing to the precise control of various morphologies and using non-cross-linked seed particles are of particular interest. Seeds particles derived from natural biopolymers are seldom applied. Hence, non-cross-linked starch-based seed could be used to fabricate the anisotropic particles by soap-free seed polymerization. Non-cross-linked starch-based seed particles were prepared by a nanoprecipitation method. Starch/polystyrene composite colloidal particles with shape-tunable were fabricated by soap-free seeded polymerization using starch-based seed. The effect of the polymerization time, monomer feed ratio and seed type were investigated. The seed particles with a single- or multi-hole structure were obtained after swelling with styrene. The resulting particles including golf-like, raspberry-like, octahedron-like and snowman-like structures, was fabricated on the polymerization process. This study firstly reports that the morphology of composite particles from golf-like to snowman-like at high monomer feed ratio using starch-based seed. At low monomer feed ratio, raspberry-like particles were obtained by surface nucleation increasing process. In addition, seed type also effect the morphology of composite particles.

Amplified Detection of Prions and Other Amyloids by RT-QuIC in Diagnostics and the Evaluation of Therapeutics and Disinfectants.

Among the most sensitive, specific and practical of methods for detecting prions are the real-time quaking-induced conversion (RT-QuIC) assays. These assays exploit the fundamental self-propagating activity of prions to amplify the presence of prion seeds by as much as a trillion-fold. The reactions can detect most of the known mammalian prion diseases, often with sensitivities greater than those of animal bioassays. RT-QuIC assays are performed in multiwell plates with fluorescence detection and have now reached the sensitivity and practicality required for routine prion disease diagnostics. Some key strains of prions within particular host species, e.g., humans, cattle, and sheep, can be discriminated by comparison of RT-QuIC responses with different recombinant prion protein substrates. The most thoroughly validated diagnostic application of RT-QuIC is in the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) using cerebrospinal fluid. Diagnostic sensitivities as high as 96% can be achieved in less than 24h with specificities of 98%-100%. The ability, if needed, to also test nasal swab samples can increase the RT-QuIC sensitivity for sCJD to virtually 100%. In addition to diagnostic applications, RT-QuIC has also been used in the testing of prion disinfectants and potential therapeutics. Mechanistically related assays are also now being developed for other protein misfolding diseases.

Preparation of Porous Poly(Styrene-Divinylbenzene) Microspheres and Their Modification with Diazoresin for Mix-Mode HPLC Separations.

By using the two-step activated swelling method, monodisperse porous poly(styrene-divinylbenzene) (P(S-DVB)) microparticles were successfully synthesized. The influence of porogens, swelling temperatures and crosslinking agents on the porosity of porous microparticles was carefully investigated. Porous P(S-DVB) microparticles were used as a packing material for high performance liquid chromatography (HPLC). Several benzene analogues were effectively separated in a stainless-steel column as short as 75 mm due to the high specific surface area of the porous microparticles. Porous P(S-DVB) microparticles were further sulfonated and subsequently modified with diazoresin (DR) via electrostatic self-assembly and UV (ultraviolet) radiation. After treatment with UV light, the ionic bonding between sulfonated P(S-DVB) and DR was converted into covalent bonding through a unique photochemistry reaction of DR. Depending on the chemical structure of DR and mobile phase composition, the DR-modified P(S-DVB) stationary phase performed different separation mechanisms, including reversed phase (RP) and hydrophilic interactions. Therefore, baseline separations of benzene analogues and organic acids were achieved by using the DR-modified P(S-DVB) particles as packing materials in HPLC. According to the π-π interactional difference between carbon rings of fullerenes and benzene rings of DR, C60 and C70 were also well separated in the HPLC column packed with DR-modified P(S-DVB) particles.

Assessment of starch-based wood adhesive quality by confocal Raman microscopic detection of reaction homogeneity.

Confocal Raman microscopy (CRM) was used to detect the reaction homogeneity of vinyl acetate grafted on starch granules and help to assess the quality of high solid content starch-based wood adhesive (HSSWA). Primarily, four experimental starch samples were investigated, and by analysis of band area ratio (carbonyl/carbohydrate) of each granule, information about reaction homogeneity was collected. The results showed that reaction extent and homogeneity were inconsistent for samples with different G values, and the distribution of ester groups on blend samples was much less uniform than grafted starch samples with the same G value, confirming that CRM was useful for determining the homogeneity of chemical modification. Afterwards, the technique was applied to research HSSWA prepared by two-stage seeded polymerization and traditional process. The distribution of ester groups was more uniform among starch granules prepared by former method, resulted in adhesive with much better performance, indicating that uniformity of polymerization was an important factor related to properties of starch-based wood adhesive.

Varying the porous structure of polystyrene/divinylbenzene beads prepared by Ugelstads activated swelling technique and examining its reversed phase HPLC properties.

Monodisperse unfunctionalized polystyrene/divinylbenzene beads were prepared via Ugelstads two-step activated swelling procedure. The modification of the porous structure was achieved in two different ways, by either changing the kind and amount of diluent or the concentration of crosslinker. Overall 10 different types of diluents, both solvent and nonsolvent types, were utilized. In all cases divinylbenzene was used as crosslinking agent in concentrations of 55% and 80%, which are commercially available, and 100%, which had to be synthesized. The size and morphology of these particles were examined with scanning electron microscopy. For the analysis of the internal porous structure inverse size exclusion chromatography was conducted. Depending on the monomer and diluent composition beads in the range of 3.4-4.5µm having a specific surface area from 90 to 1898m(2)/g were synthesized. Separation performance was then also investigated using RP-HPLC with benzene and propylbenzene as analytes. Porous and reversed-phase properties were subsequently linked to explain the observed shift in retention and efficiency. Polymers having the highest specific surface area and the smallest mean pore diameter exhibited the best performance with reduced plate height of 3.1.

Life cycle of cytosolic prions.

Prions are self-templating protein aggregates that were originally identified as the causative agent of prion diseases in mammals, but have since been discovered in other kingdoms. Mammalian prions represent a unique class of infectious agents that are composed of misfolded prion protein. Prion proteins usually exist as soluble proteins but can refold and assemble into highly ordered, self-propagating prion polymers. The prion concept is also applicable to a growing number of non-Mendelian elements of inheritance in lower eukaryotes. While prions identified in mammals are clearly pathogens, prions in lower eukaryotes can be either detrimental or beneficial to the host. Prion phenotypes in fungi are transmitted vertically from mother to daughter cells during cell division and horizontally during mating or abortive mating, but extracellular phases have not been reported. Recent findings now demonstrate that in a mammalian cell environment, protein aggregates derived from yeast prion domains exhibit a prion life cycle similar to mammalian prions propagated ex vivo. This life cycle includes a soluble state of the protein, an induction phase by exogenous prion fibrils, stable replication of prion entities, vertical transmission to progeny and natural horizontal transmission to neighboring cells. Our data reveal that mammalian cells contain all co-factors required for cytosolic prion propagation and dissemination. This has important implications for understanding prion-like properties of disease-related protein aggregates. In light of the growing number of identified functional amyloids, cell-to-cell propagation of cytosolic protein conformers might not only be relevant for the spreading of disease-associated proteins, but might also be of more general relevance under non-disease conditions.