Reversible Addition-fragmentation Chain Transfer Research Articles

Fluoropolymer-Gadolinium(III) Hybrids for Photoactivatable Dual-Mode T1-Weighted 1H MRI and 19F MRI Contrast Agents.

Multimodal imaging probes play a crucial role in overcoming the limitations associated with single-mode imaging for clinical medical diagnosis. This study focuses on the development of a photoresponsive fluorine-containing water-soluble polymer (PF) through RAFT polymerization. Subsequently, a polymer-gadolinium(III) hybrid (PF-Gd) dual-modal probe capable of T1-weighted 1H MRI and 19F MRI was synthesized via postmodification of PF with a Gd-DOTA derivative. Under physiological conditions (pH = 7.4), the hybrids exhibit UV-activated 19F NMR/MRI and enhanced 1H MRI. The inclusion of Gd3+ facilitates the acceleration of water molecule T1 relaxation, leading to high-intensity 1H MRI contrast. Leveraging the paramagnetic relaxation enhancement (PRE) effect between fluorine atoms and Gd3+, the restoration of Gd3+-accelerated 19F T2 relaxation enables precise photoactivation of 19F MRI signals, transitioning from the "OFF" to the "ON" state. This study provides an important reference for the development of hybrid systems that function as real-time diagnostic tools and offers controlled activation for multimodal imaging probes.

Thermo-responsible PNIPAM-grafted polystyrene microspheres for mesenchymal stem cells culture and detachment.

The preparation of cells is a critical step in cell therapy. To ensure the effectiveness of cells used for clinical treatments, it is essential to harvest adherent cells from the culture media in a way that preserves their high viability and full functionality. In this study, we developed temperature-responsive poly(N-isopropylacrylamide) (PNIPAM)-grafted polystyrene (PS) microspheres using reversible addition-fragmentation chain transfer polymerization. These microspheres allow for the non-destructive harvesting of cultured cells through temperature changes. The composition and physicochemical properties of the PNIPAM-grafted PS microspheres were confirmed using infrared spectroscopy, elemental analysis, dynamic light scattering, and thermogravimetric analysis.In vitroexperiments demonstrated that these microspheres exhibit excellent biocompatibility, supporting the adhesion and proliferation of various cells. Moreover, the microspheres showed good temperature responsiveness in thermosensitive detachment experiments with GFP-HepG2cells and umbilical cord mesenchymal stem cells (UC-MSCs). Additionally, through orthogonal experiments, we identified a cell detachment aid mixture that significantly improved the dispersibility of cells detached from the microspheres, enhancing the efficiency of thermosensitive cell detachment by approximately 40%. The harvested UC-MSCs retained their capacity for re-proliferation and trilineage differentiation. Consequently, the temperature-responsive microspheres developed in this study, combined with the cell detachment aid mixtures, hold great potential for large-scale culture and harvesting of therapeutic cells in clinical applications.

Polymeric nanocarrier via metabolism regulation mediates immunogenic cell death with spatiotemporal orchestration for cancer immunotherapy

The limited efficacy of cancer immunotherapy occurs due to the lack of spatiotemporal orchestration of adaptive immune response stimulation and immunosuppressive tumor microenvironment modulation. Herein, we report a nanoplatform fabricated using a pH-sensitive triblock copolymer synthesized by reversible addition-fragmentation chain transfer polymerization enabling in situ tumor vaccination and tumor-associated macrophages (TAMs) polarization. The nanocarrier itself can induce melanoma immunogenic cell death (ICD) via tertiary amines and thioethers concentrating on mitochondria to regulate metabolism in triggering endoplasmic reticulum stress and upregulating gasdermin D for pyroptosis as well as some features of ferroptosis and apoptosis. After the addition of ligand cyclic arginine-glycine-aspartic acid (cRGD) and mannose, the mixed nanocarrier with immune adjuvant resiquimod encapsulation can target B16F10 cells for in situ tumor vaccination and TAMs for M1 phenotype polarization. In vivo studies indicate that the mixed targeting nanoplatform elicits tumor ICD, dendritic cell maturation, TAM polarization, and cytotoxic T lymphocyte infiltration and inhibits melanoma volume growth. In combination with immune checkpoint blockade, the survival time of mice is markedly prolonged. This study provides a strategy for utilizing immunoactive materials in the innate and adaptive immune responses to augment cancer therapy.

Orthogonal Atom Transfer Radical Polymerization and Reversible Addition–Fragmentation Chain Transfer Polymerization for Controlled Polymer Architectures

Orthogonal Atom Transfer Radical Polymerization and Reversible Addition–Fragmentation Chain Transfer Polymerization for Controlled Polymer Architectures

Application of Sortase-Mediated Ligation for the Synthesis of Block Copolymers and Protein-Polymer Conjugates.

Sortase-mediated ligation (SML) has become a powerful tool for site-specific protein modification. However, sortaseA (SrtA) suffers from low catalytic efficiency and mediates an equilibrium reaction. Therefore, ligations with large macromolecules may be challenging. Here, the synthesis of polymeric building blocks for sortase-mediated ligation constituting peptide-polymers with either the recognition sequence for sortaseA (LPX1TGX2) or its nucleophilic counterpart (Gx) is demonstrated. The peptide-polymers are synthesized by solid-phase peptide synthesis followed by photo-iniferter (PI) reversible addition-fragmentation chain-transfer (RAFT) polymerization of various monomers. The building blocks are subsequently utilized to investigate possibilities and limitations when using macromolecules in SML. In particular, diblock copolymers are obtained even when using the orthogonal building blocks in equimolar ratio by exploiting a technique to shift the reaction equilibrium. However, ligations of two polymers can not be achieved when the degree of polymerization exceeds 100. Subsequently, C-terminal protein-polymer conjugates are synthesized. Several polymers are utilized that can replace the omnipresent polyethylene glycol (PEG) in future therapeutics. The conjugation is exemplified with a nanobody that is known for efficient neutralization of SARS-CoV-2. The study demonstrates a universal approach to polymer-LPX1TGX2 and Gx-polymer building blocks and gives insight into their application in SML.

Synthesis of magnetic polystyrene nanocomposite by emulsion polymerization using a photo-responsive emulsifier for efficient crude oil absorption

Both human health and marine life are seriously threatened by crude oil spills into bodies of water. For effective crude oil spill cleaning, we created a magnetic polystyrene (m-PS) nanocomposite. The use of magnetic nanoparticles makes crude oil absorption more environmentally friendly by making it easier to collect and recycle using an external magnetic field. To make Fe3O4 nanoparticles compatible with the hydrophobic styrene monomer used in emulsion polymerization, they were treated using a hydrophobic surface modification reaction. This alteration facilitated the grafting of polystyrene (PS) chains onto the nanoparticles, which then underwent emulsion polymerization. As an emulsifier, a light-responsive amphiphilic block copolymer containing coumarin was created via reversible addition-fragmentation chain transfer polymerization. This allowed for regulated emulsification and demulsification in response to UV stimulation. The synthesized m-PS nanocomposite demonstrated a crude oil absorption capacity of up to 2.31 times of its own weight, indicating its high efficiency for crude oil spill cleanup. The synthetic emulsifier exhibited a significantly lower critical micelle concentration compared to the commercial P105 emulsifier (0.0976 against 0.354 mg/mL, respectively), indicating higher efficiency and reduced environmental impact. For a more thorough comprehension of the reported results, we also assessed the Hofmeister effect in PS produced using commercial and synthetic emulsifiers.

Kinetics and scale inhibition application studies towards bulk and RAFT copolymerization of maleic anhydride and acrylic acid

Poly(maleic anhydride) (PMA) is commonly reckoned as a better water scale inhibitor than poly(acrylic acid) (PAA) since each maleic anhydride unit can supply two carboxylic acid groups. However, pure PMA is difficult to achieve because the steric effect of its monomer MA. Herein, we synthesize copoly(MA-AA) copolymer by bulk polymerization method (bulk-copoly(MA-AA)), which avoids the use of any solvents which have to be removed afterwards. In addition, we also synthesize copoly(MA-AA) by reversible addition-fragmentation chain transfer (RAFT) polymerization method to afford RAFT-copoly(MA-AA) with low polydispersity index (PDI) less than 1.2, and the performance of RAFT-copoly(MA-AA) in water scale inhibition is more excellent relative to bulk-copoly(MA-AA). We also synthesize other copoly(MA-AA) copolymers by varying the molar ratio of MA to AA to study the polymerization mechanism. Through the static scale inhibition experiment, it is concluded that when the concentration of copoly(MA-AA) is 80 mg/L, the scale inhibition performance of RAFT-copoly(MA-AA) can reach 96.50 % which is the best among the control samples. It is also found that only 1:1 alternating copolymerization of MA and AA could be achieved as demonstrated by 1H nuclear magnetic resonance spectra of the copolymers, evidencing the strong steric hindrance of MA for its homo-polymerization.

PH-induced morphological reversible transition from microparticles to vesicles for effective bacteria entrapment

Polymer particles with stimuli-responsive properties offer promising applications in healthcare, chemical reactors, development of artificial cells and organelles, as well as in the entrapment of bacteria. In this study, a novel biocompatible, biodegradable, and pH-responsive diblock copolymer based on polylactide (PLA) and poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) was synthesized via a metal-free one-pot/simultaneous ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) approach (ROP/RAFT). This copolymer was then employed to produce highly monodisperse microparticles using microfluidics droplet generation technique. Utilizing confocal microscopy imaging, a reversible pH-induced morphological transition from microparticles to vesicle-like structures was observed at pH 5.1. The reversible shift in morphology from microparticles to giant vesicles (Vs) in acidic environments is triggered by the protonation of amino groups of the PDPA block, rendering vesicle surfaces positively charged − an advantageous feature for attracting and engulfing negatively charged bacteria. Initial validation involved electrostatic interactions with negatively charged latex resin beads followed by assessing interaction capabilities with gram-negative bacteria, Escherichia coli (E. coli). Additionally, the reversible morphological transition of microparticles-to-vesicles was employed to study drug release at different pHs. This approach proven to be a promising strategy for targeted drug delivery and bacteria entrapment using smart pH-responsive microparticles.

Stimuli-responsive nanoparticles from RAFT dispersion polymerization-induced self-assembly (PISA) of N-phenylacrylamide copolymerized with a boronic acid-substituted derivative

Boronic acid (BA) moieties confer a variety of stimuli-response properties upon polymers. PISA is the most efficient technique for the preparation of core–shell nanoparticles (NPs), however aqueous dispersion PISA of free BA-containing monomers is complicated by the formation of the boroxine anhydride at the hydrophobic core. In the present work, dispersion reversible addition-fragmentation chain transfer (RAFT) copolymerization of a free BA-containing derivative of N-phenylacrylamide yields NP morphologies which are different to those formed from the equivalent PISA homopolymerization without BA. Depending on conditions, PISA results in spheres, rods, and worms with colloidal stability improved by using a higher fraction of the non-stimuli responsive monomer to give large compound micelles. Post-polymerization stimuli-response from the resultant PISA dispersion through hydrolysis of boroxine-rich copolymer NPs by dilution with the aqueous dispersion solvent or with water yields micron-sized worms, lamellae, and vesicles. Self-assembly to higher order morphologies is driven by the extent of hydrolysis. The resultant free BA-containing NPs becoming smaller and spherical upon basification and glucose addition.

Intelligent Supramolecular Modification for Implants: Endogenous Regulation of Bone Defect Repair in Osteoporosis.

Addressing osteoporosis-related bone defects, a supramolecular strategy is innovated for modifying carbon fiber reinforced polyether ether ketone (CF/PEEK) composites. By covalently attaching intelligent macromolecules via in situ RAFT polymerization, leveraging the unique pathological microenvironment in patients with iron-overloaded osteoporosis, intelligent supramolecular modified implant surface possesses multiple endogenous modulation capabilities. After implantation, surface brush-like macromolecules initially resist macrophage adhesion, thereby reducing the level of immune inflammation. Over time, the molecular chains undergo conformational changes due to Fe (III) mediated supramolecular self-assembly, transforming into mechanistic signals. These signals are then specifically transmitted to pre-osteoblast cell through the binding capacity of the KRSR short peptide at the molecular terminus, induced their osteogenic differentiation via the YAP/β-catenin signaling axis. Furthermore, osteoblasts secrete alkaline phosphatase (ALP), which significantly hydrolyzes phosphate ester bonds in surface macromolecular side groups, resulting in the release of alendronate (ALN). This process further improves the local osteoporotic microenvironment. This intelligent surface modification tailors bone repair to individual conditions, automatically realize multiple endogenous regulation once implanted, and truly realize spontaneous activation of a series of responses conducive to bone repair in vivo. It is evidenced by improved bone regeneration in iron-overloaded osteoporotic rabbits and supported by in vitro validations.

Rh nanoparticles confined in triphenylphosphine oxide-functionalized core-crosslinked micelles with a polyanionic shell: Synthesis, characterization, and application in aqueous biphasic hydrogenation

Core-crosslinked micelles (CCMs) with a hydrophilic polyanionic shell made of poly(sodium styrene sulfonate) chains, P(SS−Na+), a triphenylphosphine oxide-functionalized polystyrene core (TPPO@PSt) and crosslinked at the inner end of the polystyrene chains by diethylene glycol dimethacrylate (DEGDMA) were synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization as a stable TPPO@CCM-A latex. One-pot synthesis of rhodium nanoparticles (RhNPs) by the reduction of [Rh(COD)(μ-Cl)]2 in the aqueous TPPO@CCM-A latex yielded a stable RhNP-TPPO@CCM-A latex without the need of additional stabilizer or base. This Rh-loaded latex was applied to the catalytic biphasic hydrogenation of styrene under mild conditions with complete selectivity towards ethylbenzene and corrected turnover frequencies (cTOFs) ranging from 3250 to 10,010 h−1 based on the surface atoms of the RhNPs. Importantly, the catalytic phase proved recyclable after product extraction, owing to the efficient retention of the RhNPs by the core TPPO ligands.

Synthesis of Degradable Homopolymer, Gradient and Block Copolymers, and Self-Assembly via RAFT Polymerization of 4,4-Dimethyl-2-methylene-1,3-dioxolan-5-one

Synthesis of Degradable Homopolymer, Gradient and Block Copolymers, and Self-Assembly via RAFT Polymerization of 4,4-Dimethyl-2-methylene-1,3-dioxolan-5-one

Polymer functionalized antimony sulfide quantum dots for broadband optical limiting.

The rapid development of zero-dimensional quantum dots-based nanotechnology has motivated the design and synthesis of novel nano-functional materials for optoelectronic and photonic devices in recent years. Antimony sulfide (Sb2S3) quantum dots (SQDs), with an average diameter of 3.22 nm, were prepared via a top-down liquid ultrasonication exfoliation technique. Highly soluble poly(N-vinylcarbazole)-covalently functionalized SQDs (SQDs-PVK) were synthesized in situ by reversible addition fragmentation chain transfer polymerization, and embedded into a non-optically active poly(methylmethacrylate) (PMMA) matrix giving the SQDs-PVK/PMMA film. The annealed SQDs-PVK/PMMA film showed exceptional nonlinear optical performance, with large nonlinear absorption coefficients of 713.71 cm GW-1 at 532 nm and 913.60 cm GW-1 at 1064 nm, and small limiting thresholds of 1.44 J cm-2 at 532 nm and 1.08 J cm-2 at 1064 nm. These advantages make SQDs-PVK one of the promising candidates for a broadband optical limiter in both the near-infrared and visible ranges.

Swelling-assisted surface grafting strategy for multichannel antifouling membranes: Reconstruction of surface pore structure and applications in microalgae harvesting and blood purification

Membrane fouling remains a major challenge in membrane separation. The modification of hydrophilic membrane surfaces can mitigate irreversible fouling deposition, thereby improving antifouling properties. Effective surface modification strategies are essential techniques for developing highly efficient antifouling membranes. In this work, a swelling-assisted surface grafting strategy was proposed for multichannel antifouling membranes, where various lengths of polyvinylpyrrolidone (PVP) brushes were grafted on the surface of polysulfone membrane using reversible addition-fragmentation chain transfer polymerization. The successful grafting of PVP polymer brushes was confirmed using Fourier transform infrared spectrometer and X-ray Photoelectron Spectroscopy. Changes in membrane morphology and pore structure were observed via scanning electron microscope and atomic force microscope. During the grafting process, the amphiphilic macromolecules formed through grafting were selectively swelled by graft solvent, leading to the formation of mesopores in both the surface layer and sublayer of the membrane, which formed additional water transport channels. The introduction of hydrophilic polymer brushes and the change of pore structure significantly boosted the hydrophilicity and permeability of the membranes. As a result, the water contact angle decreased from 85° to 42°, accompanied by an approximate 3.24-fold increase in pure water flux (PWF). Due to superior hydrophilicity, modified membranes demonstrated exemplary performance in microalgae harvesting, boasting a microalgae retention rate nearing 100 % and low fouling resistance (2.12 × 1012 m−1). In algal filtration experiments, a confocal laser scanning microscope was employed to assess the activity of filtered algae on the membrane surface. The prepared membranes effectively maintained the bioactivity of algae while also achieving a high flux recovery rate (90.7 %) following filtration and cleaning. Furthermore, in blood cell compatibility tests, the modified membranes exhibited resistance to blood cell adhesion and sustained a low hemolysis rate (0.06 %). Overall, this strategy offers unique insights into the fabrication of antifouling surfaces and shows considerable promise for large-scale applications in microalgae harvesting and blood purification.

Innovative glycochenodeoxycholic Acid-Acrylamide Nanopolymer carriers: Regulating upper critical solution temperature on neurorehabilitation

Neurorehabilitation focuses on restoring function in patients with central and peripheral nervous system disorders, yet effective therapeutic options remain scarce. This study introduces a novel nanocopolymer, CaCO3-PAAm-GDCA, synthesized through reversible addition-fragmentation chain transfer polymerization of glycodeoxycholic acid, acrylamide, and CaCO3. This nanocopolymer exhibits a sharp and reversible insoluble-to-soluble transition in water at a temperature related to its upper critical solution temperature (UCST), which can be finely adjusted to a practical range around 37 °C, suitable for biomedical applications. The addition of β-cyclodextrin (β-CD) modulates this transition temperature by forming host-guest complexes, further enhancing the copolymer’s adaptability. When loaded with compound 1, the resulting CaCO3-PAAm-GDCA@1 significantly promoted the proliferation of damaged neuronal HT22 cells and inhibited ferroptosis through the modulation of Nrf2 and GPX4 pathways. This study provides a strong foundation for the development of neuroprotective drugs, highlighting the potential of tailored nanocopolymers in advanced neurorehabilitation therapies.

Photo‐Mediated RAFT Step‐Growth Polymerization With Diacrylate Monomers: Investigating Versatility and Oxygen Tolerance

AbstractPhotomediated reversible addition fragmentation chain transfer (RAFT) step‐growth polymerization is performed using a trithiocarbonate‐based chain transfer agent (CTA) and acrylate‐based monomers both with and without a photocatalyst. The versatility of photo‐mediated RAFT step‐growth is demonstrated by one‐pot synthesis of a graft copolymer via sequential monomer addition. Furthermore, oxygen‐tolerant photo‐mediated RAFT step‐growth is demonstrated, facilitated by the appropriate selection of photocatalyst and solvent pair (zinc tetraphenyl porphyrin [ZnTPP] and dimethyl sulfoxide [DMSO]), enabling ultralow volume polymerization under open‐air conditions.

Grafting of nonpolar polyisoprene as midblock and polar polylactide as outer block onto cellulose to produce bio-based thermoplastic elastomers

Sustainable cellulose-graft-diblock copolymers (cellulose-graft-polyisoprene-block-polylactide, MCC-g-PI-b-PLLA, MCC was chemically-modified microcrystalline cellulose) were designed and delicately synthesized for the first time by a mild and facile procedure via combining ring-opening polymerization and reversible addition-fragmentation chain transfer polymerization techniques, which conquered the difficulties in synthesis due to the distinct chemical properties among the MCC backbone, PI and PLLA blocks. Two separate glass transition temperatures were detected for MCC-g-PI-b-PLLA copolymers by differential scanning calorimetry, indicative of microphase separation, consistent with small-angle X-ray scattering and atomic force microscopy measurements. The α-form crystals of PLLA outer blocks were revealed by wide-angle X-ray diffraction measurement. The monotonic and step-cyclic tensile tests revealed that the mechanical property could be tuned by changing the molecular mass of PI midblock. The two ends of the soft PI midblock were anchored by rigid cellulose backbone and hard PLLA outer block, respectively, which served as physical crosslinking points. The rigid cellulose backbones brought the PI rubbery domains and PLLA hard domains together to form a whole hierarchical microstructure, endowing the copolymers with distinguished mechanical property. This work provided a feasible approach to producing environmental-friendly cellulose-based copolymers with fully biomass-derived feedstocks, having a profound impact on the development of sustainable polymer-based materials.

Probing the inner structure and dynamics of pH-sensitive block copolymer nanoparticles with nitroxide radicals using scattering and EPR techniques

This research emphasizes the crucial role of electron paramagnetic resonance (EPR) spectroscopy in nanoparticle analysis, showcasing its distinctive ability to probe molecular-level details. We demonstrate the synthesis and self-assembly of a new class of pH-responsive amphiphilic diblock copolymers, specifically poly[N-(2-hydroxypropyl)-methacrylamide]-block-poly[2-(diisopropylamino)ethyl methacrylate] (PHPMA-b-PDPA), incorporating 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radicals covalently bound to the hydrophilic PHPMA segment. The copolymer synthesis involved a three-step process, combining reversible addition − fragmentation chain transfer (RAFT) polymerization with carbodiimide (DCC) chemistry. TEMPO radical-containing nanoparticles (RNPs) were created using microfluidic (MF) nanoprecipitation, a technique essential for generating uniform nanoparticles with predictable biodistribution and cellular uptake. Adjusting MF protocol parameters allowed fine-tuning of RNP sizes. EPR spectroscopy confirmed the formation of core–shell RNPs, with features aligning closely with those obtained from scattering techniques like dynamic light scattering (DLS), static light scattering (SLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo-TEM). EPR spectroscopy emerges as a potent tool for molecular-level analysis of colloidal polymer systems. This study highlights the EPR-spin label method’s efficacy in probing the internal structural features and dynamics of core–shell nanoparticles, especially their response to pH-triggered disassembly. The findings open new avenues for the use of pH-responsive TEMPO-labeled diblock copolymers in controlled drug delivery applications.

PH-Triggered, Lymph Node Focused Immunodrug Release by Polymeric 2-Propionic-3-Methyl-maleic Anhydrides with Cholesteryl End Groups.

Gaining spatial control over innate immune activation is of great relevance during vaccine delivery and anticancer therapy, where one aims at activating immune cells at draining lymphoid tissue while avoiding systemic off-target innate immune activation. Lipid-polymer amphiphiles show high tendency to drain to lymphoid tissue upon local administration. Here, pH-sensitive, cholesteryl end group functionalized polymers as stimuli-responsive carriers are introduced for controlled immunoactivation of draining lymph nodes. Methacrylamide-based monomers bearing pendant 2-propionic-3-methylmaleic anhydride groups are polymerized by Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization using a cholesterol chain-transfer agent (chol-CTA). The amine-reactive anhydrides are conjugated with various amines, however, while primary amines afforded irreversible imides, secondary amines provided pH-responsive conjugates that are released upon acidification. This can be applied to fluorescent dyes for irreversibly carrier labeling or immunostimulatory Toll-like receptor (TLR) 7/8 agonists as cargos for pH-responsive delivery. Hydrophilization of remaining anhydride repeating units with short PEG-chains yielded cholesteryl-polymer amphiphiles that showed efficient cellular uptake and increased drug release at endosomal pH. Moreover, reversibly conjugated TLR 7/8 agonist amphiphiles efficiently drained to lymph nodes and increased the number of effectively maturated antigen-presenting cells after subcutaneous injection in vivo. Consequently, cholesteryl-linked methacrylamide-based polymers with pH-sensitive 2-propionic-3-methylmaleic anhydride side groups provide ideal features for immunodrug delivery.

Efficient Synthesis of Ultrahigh Molecular Weight Poly(methyl methacrylate) via Visible Light-Induced RAFT Polymerization in Deep Eutectic Solvent

Efficient Synthesis of Ultrahigh Molecular Weight Poly(methyl methacrylate) via Visible Light-Induced RAFT Polymerization in Deep Eutectic Solvent