Enzyme-instructed intramitochondrial polymerization for enhanced anticancer treatment without the development of drug-resistance.

Intracellular polymerization in living cells motivated chemists to generate polymeric structures with a multitude of possibilities to interact with biomacromolecules. However, out-of-control of the intracellular chemical reactions would be an obstacle restricting its application, providing the toxicity of non-targeted cells. Here, we reported intracellular thioesterase-mediated polymerization for selectively occurring polymerization using disulfide bonds in cancer cells. The acetylated monomers did not form disulfide bonds even under an oxidative environment, but they could polymerize into the polymeric structure after cleavage of acetyl groups only when encountered activity of thioesterase enzyme. Furthermore, acetylated monomers could be self-assembled with doxorubicin, providing doxorubicin loaded micelles for efficient intracellular delivery of drug and monomers. Since thioesterase enzymes were overexpressed in cancer cells specifically, the micelles were disrupted under activity of the enzyme and the polymerization could occur selectively in the cancer mitochondria. The resulting polymeric structures disrupted the mitochondrial membrane, thus activating the cellular death of cancer cells with high selectivity. This strategy selectively targets diverse cancer cells involving drug-resistant cells over normal cells. Moreover, the mitochondria targeting strategy overcomes the development of drug resistance even with repeated treatment. This approach provides a way for selective intracellular polymerization with desirable anticancer treatment.

A High-Performance Organic Photovoltaic System with Versatile Solution Processability.

Recently developed organic photovoltaic (OPV) materials have simultaneously closed the gaps in efficiency, stability, and cost for single-junction devices. Nonetheless, the developed OPV materials still pose big challenges in meeting the requirements for practical applications, especially regarding the prevalent issues of solution processability. Herein, a highly efficient polymer donor, named DP3, incorporating an electron-rich benzo[1,2-b:4,5-b']dithiophene unit as well as two similar and simple acceptor units is presented. Its primary objective is to enhance the interchain and/or intrachain interactions and ultimately fine-tune bulk-heterojunction microstructure. The DP3:L8-BO system demonstrates the highest power conversion efficiency (PCE) of 19.12%. This system also exhibits high-performance devices with over 18% efficiencies for five batches with various molecular weights (23.6-80.8 KDa), six different blend thicknesses (95-308 nm), differenced coating speeds (3.0-29.1 m min-1), with promising PCEs of 18.65% and 15.53% for toluene-processed small-area (0.029 cm2) cells and large-area (15.40 cm2) modules, thereby demonstrating versatile solution processability of the designed DP3:L8-BO system that is a strong candidate for commercial applications.

Polyhedral Vinyl Polymer Particles Synthesized Via Solvent-Free Radical Polymerization.

Liquid marbles (LMs) with a cubic shape are created by using various vinyl monomers as an inner liquid and polymer plates with mm size as a stabilizer. The relationship between the surface tension of the vinyl monomers and formability of the LMs is investigated. LMs can be fabricated using vinyl monomers with surface tensions of 42.7-40.3 mN m-1. The cubic polymer particles are successively synthesized via free-radical polymerizations by irradiation of the cubic LMs with UV light in a solvent-free manner. In addition, controlling the number of polymer plates per one LM, the shape of the plate or the coalescence of the LMs can lead to production of polymer particles with desired forms (e.g., Platonic and rectangular solids) that correspond to the shapes of the original LMs.

Regulation of Precise DNA Repair by Nuclear Actin Polymerization: A Chance for Improving Gene Therapy?

Although more difficult to detect than in the cytoplasm, it is now clear that actin polymerization occurs in the nucleus and that it plays a role in the specific processes of the nucleus such as transcription, replication, and DNA repair. A number of studies suggest that nuclear actin polymerization is promoting precise DNA repair by homologous recombination, which could potentially be of help for precise genome editing and gene therapy. This review summarizes the findings and describes the challenges and chances in the field.

Agave Wilt Susceptibility by Reduction of Free Hexoses in Root Tissue of Agave tequilana Weber var. azul Commercial Plants in the Fructan Accumulation Process.

Agave tequilana stems store fructan polymers, the main carbon source for tequila production. This crop takes six or more years for industrial maturity. In conducive conditions, agave wilt disease increases the incidence of dead plants after the fourth year. Plant susceptibility induced for limited photosynthates for defense is recognized in many crops and is known as "sink-induced loss of resistance". To establish whether A. tequilana is more prone to agave wilt as it ages, because the reduction of water-soluble carbohydrates in roots, as a consequence of greater assembly of highly polymerized fructans, were quantified roots sucrose, fructose, and glucose, as well as fructans in stems of agave plants of different ages. The damage induced by inoculation with Fusarium solani or F. oxysporum in the roots or xylem bundles, respectively, was recorded. As the agave plant accumulated fructans in the stem as the main sink, the amount of these hexoses diminished in the roots of older plants, and root rot severity increased when plants were inoculated with F. solani, as evidence of more susceptibility. This knowledge could help to structure disease management that reduces the dispersion of agave wilt, dead plants, and economic losses at the end of agave's long crop cycle.

Mutation-induced LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome.

Noonan syndrome patients harboring causative variants in LZTR1 are particularly at risk to develop severe and early-onset hypertrophic cardiomyopathy. In this study, we investigate the mechanistic consequences of a homozygous variant LZTR1L580P by using patient-specific and CRISPR-Cas9-corrected induced pluripotent stem cell (iPSC) cardiomyocytes. Molecular, cellular, and functional phenotyping in combination with in silico prediction identify an LZTR1L580P-specific disease mechanism provoking cardiac hypertrophy. The variant is predicted to alter the binding affinity of the dimerization domains facilitating the formation of linear LZTR1 polymers. LZTR1 complex dysfunction results in the accumulation of RAS GTPases, thereby provoking global pathological changes of the proteomic landscape ultimately leading to cellular hypertrophy. Furthermore, our data show that cardiomyocyte-specific MRAS degradation is mediated by LZTR1 via non-proteasomal pathways, whereas RIT1 degradation is mediated by both LZTR1-dependent and LZTR1-independent pathways. Uni- or biallelic genetic correction of the LZTR1L580P missense variant rescues the molecular and cellular disease phenotype, providing proof of concept for CRISPR-based therapies.

Dual-reactive single-chain polymer nanoparticles for orthogonal functionalization through active ester and click chemistry.

Glucose has been extensively studied as a targeting ligand on nanoparticles for biomedical nanoparticles. A promising nanocarrier platform are single-chain polymer nanoparticles (SCNPs). SCNPs are well-defined 5-20 nm semi-flexible nano-objects, formed by intramolecularly crosslinked linear polymers. Functionality can be incorporated by introducing labile pentafluorophenyl (PFP) esters in the polymer backbone, which can be readily substituted by functional amine-ligands. However, not all ligands are compatible with PFP-chemistry, requiring different ligation strategies for increasing versatility of surface functionalization. Here, we combine active PFP-ester chemistry with copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry to yield dual-reactive SCNPs. First, the SCNPs are functionalized with increasing amounts of 1-amino-3-butyne groups through PFP-chemistry, leading to a range of butyne-SCNPs with increasing terminal alkyne-density. Subsequently, 3-azido-propylglucose is conjugated through the glucose C1- or C6-position by CuAAC click chemistry, yielding two sets of glyco-SCNPs. Cellular uptake is evaluated in HeLa cancer cells, revealing increased uptake upon higher glucose-surface density, with no apparent positional dependance. The general conjugation strategy proposed here can be readily extended to incorporate a wide variety of functional molecules to create vast libraries of multifunctional SCNPs.

Molecularly imprinted polymers in the analysis of chlorogenic acid: A review.

Chlorogenic acid, a phenolic compound, is prevalent across various plant species and has been known for its pharmacological advantages. Health care experts have identified chlorogenic acid as a potential biomarker for treatment of a wide range of illnesses. Therefore, achieving efficient extraction and analysis of chlorogenic acid from plants and their products has become essential. Molecularly imprinted polymers (MIPs) are highly effective adsorbent for the extraction of chlorogenic acid from complex matrices. Currently, there is a lack of comprehensive review article that consolidate the methods utilized for the purification of chlorogenic acid through molecular imprinting. In this context, we have surveyed the common approaches employed in preparing MIPs specifically designed for the analysis of chlorogenic acid, including both conventional and newly developed. This review discusses the advantages, limitations of polymerization techniques and proposed strategies to produce more efficient MIPs for chlorogenic acid enrichment in complex samples. Additionaly, we present advanced imprinting methods for designing MIPs, which improve the adsorption capacity, sensitivity and selectivity towards chlorogenic acid.

Organic nanoparticles with tunable size and rigidity by hyperbranching and cross-linking using microemulsion ATRP.

Unlike inorganic nanoparticles, organic nanoparticles (oNPs) offer the advantage of "interior tailorability," thereby enabling the controlled variation of physicochemical characteristics and functionalities, for example, by incorporation of diverse functional small molecules. In this study, a unique inimer-based microemulsion approach is presented to realize oNPs with enhanced control of chemical and mechanical properties by deliberate variation of the degree of hyperbranching or cross-linking. The use of anionic cosurfactants led to oNPs with superior uniformity. Benefitting from the high initiator concentration from inimer and preserved chain-end functionality during atom transfer radical polymerization (ATRP), the capability of oNPs as a multifunctional macroinitiator for the subsequent surface-initiated ATRP was demonstrated. This facilitated the synthesis of densely tethered poly(methyl methacrylate) brush oNPs. Detailed analysis revealed that exceptionally high grafting densities (~1 nm-2) were attributable to multilayer surface grafting from oNPs due to the hyperbranched macromolecular architecture. The ability to control functional attributes along with elastic properties renders this "bottom-up" synthetic strategy of macroinitiator-type oNPs a unique platform for realizing functional materials with a broad spectrum of applications.

Physical properties of experimental light-curing pattern resins based on poly (n-butyl methacrylate) or poly(iso-butyl methacrylate).

Experimental light-curing pattern resins were fabricated to produce pattern resin materials with adequate dimensional stability. The light-curing pattern resins consisted of poly(n-butyl methacrylate) or poly(iso-butyl methacrylate) (PiBMA) polymers and methacrylate monomers. The physical properties, amount of residual ash after burning, Vickers hardness, flexural strength, and volumetric polymerization shrinkage of each material were determined. The data obtained for the prepared resins were compared with those of a commercially available pattern resin, Palavit G (PG). A lower amount of residual ash was observed for some of the prepared resins than for PG. The Vickers hardness and flexural strength values of all experimental resins were lower than those of PG. The volumetric polymerization shrinkage of all the experimental resins based on PiBMA was lower than that of PG. These results suggest that acrylic light-curing resin materials based on PiBMA may be useful for patterning and indexing during soldering.

Living Hybrid Exciton Materials: Enhanced Fluorescence and Chiroptical Properties in Living Supramolecular Polymers with Strong Frenkel/Charge-Transfer Exciton Coupling.

A family of chiral perylene diimides (PDIs) was newly developed as excellent circularly polarized luminescence (CPL) materials. They are asymmetrically derivatized with a double-alkyl-chained L- or D-glutamate unit and a linear or branched alkyl chain. When water is added to the tetrahydrofuran (THF) solution of glutamate-PDI-linear-alkyl chain compounds, kinetically formed H-aggregates are formed in globular nanoparticles (NPs). These NPs undergo spontaneous transformation into thermodynamically stable nanotubes via helical nanostructures, which showed structured broad spectra originating from the strong coupling of delocalized Frenkel excitations (FE) and charge transfer excitations (CTE). Significant enhancement of circular dichroism (CD), fluorescence quantum yield, and circularly polarized luminescence (CPL) with luminescence dissymmetry factor (glum) are observed during the transformation of NPs to the FE/CTE-coupled helical and tubular structures. This transformation process is significantly accelerated by applying physical stimuli, i.e., ultrasonication or adding helical aggregates as seed crystals, a feature unique to living supramolecular polymerization. Meanwhile, the branched chain-containing PDIs only form H-aggregates and did not show FE/CTE hybrid exciton states with living supramolecular polymerization properties. This study unveils that suitably designed chiral PDI derivatives show FE/CTE coupling accompanied by high fluorescence quantum yields, enhanced chiroptical properties, and supramolecular living polymerization characteristics.

Wiring Covalent Organic Frameworks with Conducting Polymers.

Covalent organic frameworks are a class of crystalline porous polymers formed by linking organic units into periodically aligned skeletons and pores. Here we report a strategy for wiring these frameworks with conducting polymers via wall engineering and polymerization. We anchored each edge site with one pyrrole unit, which is densely packed along the z direction yet protruded from pore walls. This assembly enables the polymerization of pyrrole units to form polypyrrole and creates a new polypyrrole chain conformation. The resultant framework constitutes six single file polypyrrole chains in each pore and develop spatially segregated yet built-in single molecular wires with exceptional stable polarons. Hall effect measurements revealed that the materials are p-type semiconductors, increase conductivity by eight orders of magnitude compared to the pristine frameworks, and achieve a carrier mobility as large as 13.2 cm2 V-1 s-1. Our results open an avenue to π electronic frameworks by interlayer molecular wiring with conducting polymers.

A Versatile Reversible, Degenerative Chain Transfer Mechanism for the Catalytic Living Ring-Opening Metathesis Polymerization.

Most metathesis polymers based on norbornene derivatives carry a vinyl end group. Here we show that these vinyl end groups readily undergo a degenerative exchange of the terminal methylene unit in the presence of sub-stoichiometric amounts of a propagating metathesis polymer carrying a Grubbs ruthenium complex. We show that this degenerative exchange can be exploited in synthesizing ROMP polymers in a catalytic living fashion. Chain transfer agents based on styrene, or monosubstituted conjugated 1,3 diene derivatives are used as initiating sites for the catalytic living polymerization. Suitable derivatives of these chain transfer agents not only allow the linear living growth of polymers but also the synthesis of block copolymers from macro-initiators or star polymers from multi-functional chain transfer agents. This reversible exchange mechanism offers a cheaper, greener, and more sustainable alternative for the synthesis of living ROMP polymers compared to the classical synthetic route.

A Facile Approach to Construct Novel Polyesters as Soft Midblock for Thermoplastic Elastomers.

The development of innovative synthetic strategies to create functional polycaprolactones is highly demanded for advanced material applications. In this contribution, we reported a facile synthetic strategy to prepare a class of CL-based monomers (R-TO) derived from epoxides. They readily polymerize via well-controlled ring-opening polymerization (ROP) to afford a series of polyesters P(R-TO) with high molecular weight (Mn up to 350 kDa). Sequential addition copolymerization of MTO and L-lactide (L-LA) allowed to access of a series of ABA triblock copolymers with composition-dependent mechanical properties. Notably, P(L-LA)100-b-P(MTO)500-b-P(L-LA)100 containing the amorphous P(MTO) segment as a soft midblock and crystalline P(L-LA) domain as hard end block behaved as an excellent thermoplastic elastomer (TPE) with high elongation at break (1438 ± 204%), tensile strength (23.5 ± 1.7 MPa), and outstanding elastic recovery (>88%).

Asymmetric Kinetic Resolution Polymerization of Racemic Lactide Mediated by Axial-Chiral Thiourea/Phosphazene Binary Organocatalyst.

Asymmetric kinetic resolution polymerization (AKRP) provides an ideal way to obtain highly isotactic polylactide (PLA) with superior thermal-mechanical properties from racemic lactide (rac-LA). However, the development of a new catalytic system with concurrent high activity and selectivity at ambient temperature remains a great challenge. Here, a series of simple and effective binary organocatalytic pairs containing axial-chiral thioureas and commercially available phosphazene bases were designed. These chiral binary organocatalytic pairs allow for both high polymerization activity and moderate enantioselectivity for AKRP of rac-LA at room temperature, yielding semi-crystalline and metal-free stereoblock PLA with a melting temperature as high as 186 °C. The highest kinetic resolution coefficient (krel) of 8.5 at 47% conversion was obtained, and D-LA was preferentially polymerized via kinetic resolution with a maximum selectivity factor (kD/kL) of 18.1, indicating that an enantiomorphic site control mechanism (ESC) was involved.

Integrated Framework to Model Microstructure Evolution and Decipher the Microstructure-Property Relationship in Polymeric Porous Materials.

Unraveling the microstructure-property relationship is crucial for improving material performance and advancing the design of next-generation structural and functional materials. However, this is inherently challenging because it requires both the comprehensive quantification of microstructural features and the accurate assessment of corresponding properties. To meet these requirements, we developed an efficient and comprehensive integrated modeling framework, using polymeric porous materials as a representative model system. Our framework generates microstructures using a physics-based phase-field model, characterizes them using various average and localized microstructural features, and evaluates microstructure-aware properties, such as effective diffusivity, using an efficient Fourier-based perturbation numerical scheme. Additionally, the framework incorporates machine learning methods to decipher the intricate microstructure-property relationships. Our findings indicate that the connectivity of phase channels is the most critical microstructural descriptor for determining effective diffusivity, followed by the domain shape represented by curvature distribution, while the domain size has a minor impact. This comprehensive approach offers a novel framework for assessing microstructure-property relationships in polymer-based porous materials, paving the way for the development of advanced materials for diverse applications.

Dynamic BTB-domain filaments promote clustering of ZBTB proteins.

The formation of dynamic protein filaments contributes to various biological functions by clustering individual molecules together and enhancing their binding to ligands. We report such a propensity for the BTB domains of certain proteins from the ZBTB family, a large eukaryotic transcription factor family implicated in differentiation and cancer. Working with Xenopus laevis and human proteins, we solved the crystal structures of filaments formed by dimers of the BTB domains of ZBTB8A and ZBTB18 and demonstrated concentration-dependent higher-order assemblies of these dimers in solution. In cells, the BTB-domain filamentation supports clustering of full-length human ZBTB8A and ZBTB18 into dynamic nuclear foci and contributes to the ZBTB18-mediated repression of a reporter gene. The BTB domains of up to 21 human ZBTB family members and two related proteins, NACC1 and NACC2, are predicted to behave in a similar manner. Our results suggest that filamentation is a more common feature of transcription factors than is currently appreciated.

Polymerization of ZBTB transcription factors regulates chromatin occupancy.

BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6's broad-complex, tramtrack, and bric-à-brac (BTB) domain. The BTB domains of other proteins, including a large class of TFs, have similar architectures and symmetries, raising the possibility that additional BTB proteins self-assemble into higher-order structures. Here, we surveyed 189 human BTB proteins with a cellular fluorescent reporter assay and identified 18 ZBTB TFs that show evidence of polymerization. Through biochemical and cryoelectron microscopy (cryo-EM) studies, we demonstrate that these ZBTB TFs polymerize into filaments. We found that BTB-domain-mediated polymerization of ZBTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites, leading to repression of target genes. Our results reveal a role of higher-order structures in regulating ZBTB TFs and suggest an underappreciated role for TF polymerization in modulating gene expression.

The growth rate of senile plaques is determined by the competition between the rate of deposition of free Aß aggregates into plaques and the autocatalytic production of free Aß aggregates.

The formation of amyloid beta (Aß) deposits (senile plaques) is one of the hallmarks of Alzheimer's disease (AD). This study investigates what processes are primarily responsible for their formation. A model is developed to simulate the diffusion of amyloid beta (Aß) monomers, the production of free Aß aggregates through nucleation and autocatalytic processes, and the deposition of these aggregates into senile plaques. The model suggests that efficient degradation of Aß monomers alone may suffice to prevent the growth of senile plaques, even without degrading Aß aggregates and existing plaques. This is because the degradation of Aß monomers interrupts the supply of reactants needed for plaque formation. The impact of Aß monomer diffusivity is demonstrated to be small, enabling the application of the lumped capacitance approximation and the derivation of approximate analytical solutions for limiting cases with both small and large rates of Aß aggregate deposition into plaques. It is found that the rate of plaque growth is governed by two competing processes. One is the deposition rate of free Aß aggregates into senile plaques. If this rate is small, the plaque grows slowly. However, if the rate of deposition of Aß aggregates into senile plaques is very large, the free Aß aggregates are removed from the intracellular fluid by deposition into the plaques, leaving insufficient free Aß aggregates to catalyze the production of new aggregates. This suggests that under certain conditions, Aß plaques may offer neuroprotection and impede their own growth. Additionally, it indicates that there exists an optimal rate of deposition of free Aß aggregates into the plaques, at which the plaques attain their maximum size.

Volumetric Additive Manufacturing of Dicyclopentadiene by Solid-State Photopolymerization.

Polymerization in the solid state is generally infeasible due to restrictions on mobility. However, in this work, the solid-state photopolymerization of crystalline dicyclopentadiene is demonstrated via photoinitiated ring-opening metathesis polymerization. The source of mobility in the solid state is attributed to the plastic crystal nature of dicyclopentadiene, which yields local short-range mobility due to orientational degrees of freedom. Polymerization in the solid state enables photopatterning, volumetric additive manufacturing of free-standing structures, and fabrication with embedded components. Solid-state photopolymerization of dicyclopentadiene offers a new paradigm for advanced and freeform fabrication of high-performance thermosets.