Star-shaped Copolymers Research Articles

Robust and Reversible Thermal/Electro-Responsive Supramolecular Polymeric Adhesives via Synergistic Hydrogen-Bonds and Ionic Junctions.

Adhesive conducting elastomers are rising materials towards cutting-edge applications in wearable and implantable soft electronics. Yet, engineering the conductive adhesives with robust and tunable interfacial bonding strength is still in its infancy stage. We herein identify a structurally novel supramolecular polymer scaffold, characterized by synergistic coexistence of hydrogen-bonding (H-bonding) interactions and electrostatic ionic junctions, endowing the robust and tunable elastic conducting adhesives with remarkable thermal/electro-responsive performance. H-bonding association and electrostatic interaction play orthogonal yet synergistic roles in the strong supramolecular adhesive formation, serving as the leveraging forces for opposing both cohesion and adhesion energy. To do so, six-arm star-shaped random copolymers P(DAP-co-Thy-co-MBT)6 are strategically designed, bearing H-bonding PDAP (poly(diaminopyridine acrylamide)) and PThy (poly(thymine)) segments, which can form hetero-complementary DAP/Thy H-bonding association, along with conductive poly(ionic liquid)s segment: PMBT, (poly(1-[2-methacryloylethyl]-3-methylimidazolium bis(trifluoromethane)-sulfonamide)). DAP/Thy H-bonding association, along with electrostatic ionic interaction, can yield dual supramolecular forces crosslinked polymeric networks with robust cohesion energy. Moreover, coexistence of poly(ionic liquid)s can impact and interfere the configuration of H-bonding association, liberate more free DAP and Thy motifs to form H-bonds towards substrate, affording strong surface adhesion in a synergistic manner. This work demonstrates a significant forward step towards potential adhesives devoted to hybrid electronic devices.

Metal-free ring-opening polymerization for the synthesis of biocompatible star-shaped block copolymers with controllable architecture

Star-shaped block copolymers (SBCs) have sparked interest as efficient cargo carriers due to their high loading capacity, decreased burst effects through sustained release, and maintained stability in dilute aqueous solution. Despite these advantages, the practical usage of SBCs is hindered by their challenging synthesis processes that often utilize metal-based catalysts at high temperatures. Herein we report the tailored synthesis of 3-, 4-, and 6-arm polycaprolactone-b-poly(ethylene glycol), PCL-b-PEG, SBCs using diphenyl phosphate as a friendlier, more sustainable non-metallic catalyst. Nuclear magnetic resonance (NMR) analysis confirms the molecular architecture of SBCs and gel permeation chromatography (GPC) is used to elucidate trends in molar mass when the number of arms within the SBCs is tuned, while dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) studies provide insights into aggregation behavior. Critical aggregation concentration (CAC) values, as measured by fluorescence spectroscopy, demonstrated that the 4-arm and 6-arm SBCs have greater stability than the 3-arm SBC. Biocompatibility assessment indicated minimal cytotoxicity of the nanoaggregates, even at high concentration, making these PCL-b-PEG SBCs potentially safe and sustainable vehicles for biomedical release applications.

Hydrodynamic Properties and LCST Behavior of Six-Armed Star-Shaped Polymers with Arms of a Diblock Copolymer of Poly-2-Ethyl-2-Oxazine and Poly-2-Isopropyl-2-Oxazine

Star-shaped six-arm polymers with arms of the block copolymers of poly-2-ethyl-2-oxazine and poly-2-isopropyl-2-oxazine were synthesized. The branching center was hexaase[26]cyclophane. The prepared samples differed in the order of block attachment to the core. Molar masses of the two samples were 14200 and 21500 g⋅mol−1. The fractions of poly-2-ethyl-2-oxazine monomers in the arms were 61 and 65%, respectively. It was shown that the arms were strongly folded. Water-salt solutions of the star-shaped block copolymers exhibited thermoresponsiveness. The difference in the phase separation temperatures for the studied samples was caused by the differences in their molar masses and the different contents of poly-2-ethyl- and poly-2-isopropyl-2-oxazine blocks. The concentration dependences of the phase separation temperatures for the synthesized star-shaped copolymers coincided with those for the arms, despite the fact that the molecular masses of the stars and their arms differed by factor of near 6. The addition of NaCl to the aqueous of solutions of the star copolymers did not lead to significant changes in their characteristics. No influence of the order of the block attachment to the core on the molecule conformation and on the thermoresponsive behavior was found.

Ultrasmall Inorganic Mesoporous Nanoparticles: Preparation, Functionalization, and Application.

Ultrasmall mesoporous nanoparticles (<50nm), a unique porous nanomaterial, have been widely studied in many fields in the last decade owing to the abundant advantages, involving rich mesopores, low density, high surface area, numerous reaction sites, large cavity space, ultrasmall size, etc. This paper presents a review of recent advances in the preparation, functionalization, and applications of ultrasmall inorganic mesoporous nanoparticles for the first time. The soft monomicelles-directed method, in contrast to the hard-template and template-free methods, is more flexible in the synthesis of mesoporous nanoparticles. This is because the amphiphilic micelle has tunable functional blocks, controlled molecule masses, configurations and mesostructures. Focus on the soft micelle directing method, monomicelles could be classified into four types, i.e., the Pluronic-type block copolymer monomicelles, laboratory-synthesized amphiphilic block copolymers monomicelles, the single-molecule star-shaped block copolymer monomicelles, and the small-molecule anionic/cationic surfactant monomicelles. This paper also reviews the functionalization of the inner mesopores and the outer surfaces, which includes constructing the yolkshell structures (encapsulated nanoparticles), anchoring the active components packed on the shell and building an asymmetric Janus architecture. Then, several representative applications, involving catalysis, energy storage, and biomedicines are presented. Finally, the prospects and challenges of controlled synthesis and large-scale applications of ultrasmall mesoporous nanoparticles in the future are foreseen.

Degradable 4D-printed hydration-driven actuators from a single family of amphiphilic star-shaped copolymers

Actuators are largely used in biomedical applications in the presence of sensitive live cells or biomolecules, which makes actuators triggered by water uptake highly appealing. Dual-material printing and hydration driven expansion is a method of choice to produce such actuators, but mostly rely of non-degradable polymers or on the combination of polymers of different nature that may lead to interface incompatibilities. To overcome this challenge, we report here on two photocrosslinkable resins based on a single family of degradable hydrophilic or hydrophobic star-shaped poly(ethylene glycol)-poly(lactide) copolymers. The two materials are first printed individually and characterized to ensure that their properties enable the printing of dual material objects by stereolithographic digital-light processing. Dual-materials actuators are then printed by sequential switching of the hydrophobic and hydrophilic resin baths. Objects of simple and complex shapes are easily obtained and exhibit rapid actuation (<60 s) upon hydration. The swelling-induced shape changes are accurately reproduced by numerical modeling of the printed geometries using the obtained material swelling properties. This set of results offers new perspectives to develop 4D-printed temporary medical devices.

Synthesis of thermo-responsive polymer gels composed of star-shaped block copolymers by copper-catalyzed living radical polymerization and click reaction

ABSTRACT In recent times, there has been a significant surge in research interest surrounding thermo-responsive water-soluble polyacrylamides, primarily due to their intriguing capability to undergo significant solubility changes in water. These polymers exhibit the remarkable ability to shift from a soluble to an insoluble state in response to temperature variations. The capacity of these polymers to dynamically respond to temperature changes opens up exciting avenues for designing smart materials with tunable properties, amplifying their utility across a spectrum of scientific and technological applications. Researchers have been particularly captivated by the potential applications of thermo-responsive water-soluble polyacrylamides in diverse fields such as drug delivery, gene carriers, tissue engineering, sensors, catalysis, and chromatography separation. This study reports the construction and functionalization of polymer gels consisting of a polymer network of polyacrylamide derivatives with nano-sized structural units. Specifically, thermo-responsive polymer gels were synthesized by combining well-defined star-shaped polymers composed of polyacrylamide derivatives with a multifunctional initiator and linking method through a self-accelerating click reaction. The polymerization system employed a highly living approach, resulting in polymer chains characterized by narrow molecular weight distributions. The method’s high functionality facilitated the synthesis of a temperature-responsive block copolymer gel composed of N-isopropyl acrylamide (NIPA) and N-ethyl acrylamide (NEAA). The resulting polymer gel, comprising star-shaped block copolymers of NIPA and NEAA, showcases smooth volume changes with temperature jumps.

Additive-anchored thermoresponsive nanoscale self-assembly generation in normal and reverse Tetronics®.

Self-assembly of ethylene oxide (EO)-propylene oxide (PO)-based star-shaped block copolymers (BCPs) in the presence of different kinds of additives is investigated in an aqueous solution environment. Commercially available four-armed BCPs, namely Tetronics® (normal: T904 with EO as the terminal end block; and reverse: T90R4 with PO as the terminal end block), each with 40%EO, are used. The effect of various additives such as electrolytes (NaCl and Na2SO4), nonelectrolyte polyols (glucose and sorbitol), and ionic surfactants (viz. anionic-sodium dodecyl sulfate (SDS), cationic-dodecyltrimethylammonium bromide (DTAB) and zwitterionic dodecyldimethylammonium propane sulfonate (C12PS)) on these BCPs is examined to observe their influence on micellization behaviour. The presence of salts and polyols displayed interesting phase behaviour, i.e., the cloud point (CP) was decreased, the water structure was affected and the micelles were dehydrated by expelling water molecules, and thus they were likely to promote micelle formation/growth. In contrast, ionic surfactants in small amounts interacted with the BCPs and showed an increase in CPs thereby forming mixed micelles with increasing charges and decreasing micellar sizes, finally transforming to small surfactant-rich mixed micelles. Molecular interactions such as electrostatic and hydrogen bonding involved within the examined entities are put forth employing a computational simulation approach using the Gaussian 09 window for calculation along with the GaussView 5.0.9 programming software using the (DFT)/B3LYP method and 3-21G basis set. The hydrodynamic diameter (Dh) of the micelles is examined using dynamic light scattering (DLS), while the various micellar parameters inferring the shape/geometry are obtained using small-angle neutron scattering (SANS) by the best fitting of the structure factors. It is observed that 10 w/v% T904 remains as spherical micelles with some micellar growth under physiological conditions (37 °C), while 10 w/v% T90R4 remains as unimers and forms spherical micelles in the presence of additives at 37 °C. Furthermore, the additive-induced micellar systems are tested as developing nanovehicles for anticancer (curcumin, Cur) drug solubilization using UV-vis spectroscopy, which shows a prominent increase in absorbance with enhanced solubilization capacity. Additionally, the cytotoxic effect of Cur loaded on the BCP micelles in HeLa cells is studied through confocal microscopy by capturing fluorescence images that depict HeLa cell growth inhibition under the influence of additive-induced micellar systems.

Thermo-responsive injectable hydrogels from linear and star-shaped block copolymers composed of amino acid-derived vinyl polymer and poly(ethylene glycol) for biomedical applications

Injectable hydrogels were developed from linear and star-shaped thermo-responsive amino acid-derived vinyl polymer/polyethylene glycol block copolymers, and revealing their usefulness as three-dimensional scaffolds for biological applications.

Harboring organocatalysts in a star-shaped block copolymer for micellar catalysis and emulsion catalysis

Conducting an asymmetric aldol reaction in both micelles and emulsions with high interfacial reactivity and stereoselectivity is achieved by incorporating an organocatalyst in the inherently hydrophobic center of a star-shaped polymer.

Ambipolar charge-trapping in self-assembled nanostructures of a supramolecular miktoarm star-shaped copolymer with a zinc phthalocyanine core

Supramolecular miktoarm star-shaped copolymers with a zinc phthalocyanine core exhibit phase-separated nanostructures that enhance ambipolar charge-trapping capabilities in the organic field-effect transistor memory devices.

Flexible Poly(vinyl chloride) with Durable Antibiofouling Property via Blending Star-Shaped Amphiphilic Poly(ε-caprolactone)-block-poly(methacryloxyethyl sulfobetaine).

Flexible poly(vinyl chloride) (PVC) plastics have been widely used in medical devices, but the preparation of antibiofouling flexible PVC materials that can maintain their antibiofouling performance when suffering deformation is still a challenge. In this work, we synthesized a series of amphiphilic star-shaped three-arm block copolymers SPCL-b-PSB, consisting of hydrophobic inner blocks poly(ε-caprolactone) (PCL) and hydrophilic outer blocks poly(methacryloxyethyl sulfobetaine) (PSB). Then, flexible PVC films were prepared by blending SPCL-b-PSB with PVC and plasticizer. Benefiting from the specific star-shaped topological structure of SPCL-b-PSB, hydrophilic PSB blocks of the copolymer could efficiently migrate to the surface of the film via annealing treatment, which give the film surface excellent hydrophilicity, while the latch-like entanglements between hydrophobic PCL blocks and PVC give the hydrophilic surface excellent stability. Antibiofouling properties of the blended films were investigated. The optimized blended film could reduce ∼94% of bovine serum albumin adsorption, ∼ 87% of lysozyme adsorption, and ∼89% of platelet adhesion and resist bacterial adhesion effectively. What is more, the blended films could maintain their antibiofouling performance when suffering stretching, rubbing, or bending. More than 86% of bovine serum albumin adsorption could be reduced, even when the film was stretched by 50%. This work provides a new strategy for the preparation of durable antibiofouling flexible plastics.

Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes.

Cannabidiol (CBD) is a promising drug candidate with pleiotropic pharmacological activity, whose low aqueous solubility and unfavorable pharmacokinetics have presented obstacles to its full clinical implementation. The rational design of nanocarriers, including niosomes for CBD encapsulation, can provide a plausible approach to overcoming these limitations. The present study is focused on exploring the feasibility of copolymer-modified niosomes as platforms for systemic delivery of CBD. To confer steric stabilization, the niosomal membranes were grafted with newly synthesized amphiphilic linear or star-shaped 3- and 4-arm star-shaped copolymers based on polyglycidol (PG) and poly(ε-caprolactone) (PCL) blocks. The niosomes were prepared by film hydration method and were characterized by DLS, cryo-TEM, encapsulation efficacy, and in vitro release. Free and formulated cannabidiol were further investigated for cytotoxicity and pro-apoptotic and anti-inflammatory activities in vitro in three human tumor cell lines. The optimal formulation, based on Tween 60:Span60:Chol (3.5:3.5:3 molar ration) modified with 2.5 mol% star-shaped 3-arm copolymer, is characterized by a size of 235 nm, high encapsulation of CBD (94%), and controlled release properties. Niosomal cannabidiol retained the antineoplastic activity of the free agent, but noteworthy superior apoptogenic and inflammatory biomarker-modulating effects were established at equieffective exposure vs. the free drug. Specific alterations in key signaling molecules, implicated in programmed cell death, cancer cell biology, and inflammation, were recorded with the niosomal formulations.

Synthesis and Self-assembly of a Novel Amphiphilic Tri-arm Star-shaped Copolymer Poly(ethylene oxide)-b-Poly(ε-caprolactone)

Abstract:Amphiphilic tri-arm star-shaped copolymers, poly(ethylene oxide)-b-poly(ε-caprolactone) PEO3-b-PCL3, with different poly (ε-caprolactone) (PCL) molecular weights were successfully synthesized by ring-opening polymerization (ROP). Firstly, the tri-arm star-shaped PEO3 was prepared by ROP of trimethylolpropane and ethylene oxide (EO). The ring-opening polymerization (ROP) of ε- caprolactone (CL) was initiated using the tri-arm star-shaped PEO3 with the hydroxyl group as macroinitiator and Sn(Oct)2 as a catalyst. Amphiphilic tri-arm star-shaped copolymers PEO3-b-PCL3 were obtained. By changing the ratio of monomer and macroinitiator, a series of PEO3-b-PCL3 were prepared with a well-defined structure, molecular weight control, and narrow molecular weight distribution. The expected intermediates and final products were confirmed by 1H NMR and Gel Permeation Chromatography (GPC) analyses. In addition, the sizes and morphologies of the obtained micelles with different PCL segment lengths were investigated with dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. It was found that the self-assembly morphologies were spherical micelle in aqueous solution.

Multi-Stimuli Responsive Sequence Defined Multi-Arm Star Diblock Copolymers for Controlled Drug Release.

Star-shaped polymeric materials provide very high efficiency toward various engineering and biomedical applications. Due to the absence of straightforward and versatile synthetic protocols, the synthesis of sequence-defined star-shaped (co)polymers has remained a major challenge. Here, a facile approach is developed that allows synthesis of a series of unprecedented discrete, multifunctional four-, six-, and eight-arm star-shaped complex macromolecular architectures based on a well-defined triple (thermo/pH/light)-stimuli-responsive poly(N-isopropylacrylamide)-block-poly(methacrylic acid)-umbelliferone (PNIPAM-b-PMAA)n-UMB diblock copolymer, based on temperature responsive PNIPAM segment, pH-responsive PMAA segment, and photoresponsive UMB end groups. Thus, developed star-shaped copolymers self-assemble in water to form spherical nanoaggregates of diameter 90 ± 20 nm, as measured by FESEM. The star-shaped copolymer's response to external stimuli has been assessed against changes in temperature, pH, and light irradiation. The star-shaped copolymer was employed as a nanocarrier for pH responsive release of an anticancer drug, doxorubicin. This study opens up new avenues for efficient star-shaped macromolecular architecture construction for engineering and biomedical applications.

Multi-Armed Star-Shaped Block Copolymers of Poly(ethylene glycol)-Poly(furfuryl glycidol) as Long Circulating Nanocarriers.

Multi-arm star-shaped block copolymers with precisely tuned nano-architectures are promising candidates for drug delivery. Herein, we developed 4- and 6-arm star-shaped block copolymers consisting of poly(furfuryl glycidol) (PFG) as the core-forming segments and biocompatible poly(ethylene glycol) (PEG) as the shell-forming blocks. The polymerization degree of each block was controlled by adjusting the feeding ratio of a furfuryl glycidyl ether and ethylene oxide. The size of the series of block copolymers was found to be less than 10 nm in DMF. In water, the polymers showed sizes larger than 20 nm, which can be related to the association of the polymers. The star-shaped block copolymers effectively loaded maleimide-bearing model drugs in their core-forming segment with the Diels-Alder reaction. These drugs were rapidly released upon heating via a retro Diels-Alder step. When the star-shaped block copolymers were injected intravenously in mice, they showed prolonged blood circulation, with more than 80% of the injected dose remaining in the bloodstream at 6 h after intravenous injection. These results indicate the potential of the star-shaped PFG-PEG block copolymers as long-circulating nanocarriers.

Phosphorus-Containing Polymers as Sensitive Biocompatible Probes for 31P Magnetic Resonance

The visualization of organs and tissues using 31P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3-400 kg·mol-1, including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM-g-PMPC) or cyclotriphosphazene-derived cores (CTP-g-PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP-g-PMPC (56) and PAMAM-g-PMPC (44). The 31P T1 and T2 relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive 31P MR probes for biomedical applications.

A Star-Shaped Copolymer with Tetra-Hydroxy-Phenylporphyrin Core and Four PNIPAM-b-PMAGA Arms for Targeted Photodynamic Therapy.

The novel thermosensitive star-shaped tetra-hydroxy-phenylporphyrin-cored (THPP) double hydrophilic poly(N-isopropylacrylamide)-b-poly(methylacrylamide glucose) block copolymers (THPP-(PNIPAM-b-PMAGA)4) were synthesized via the reversible addition-fragmentation chain transfer (RAFT) polymerization. Notably, the low critical solution temperatures (LCSTs) of THPP-(PNIPAM-b-PMAGA)4 were above normal body temperature (37 °C) which depended on the hydrophilic PMAGA contents of copolymers. When the temperature was higher than the LCST of the copolymer, the copolymer could be neutralized into micelles in aqueous and could be coated with antitumor drugs and released around tumor cells. The MTT study indicated that THPP-(PNIPAM-b-PMAGA)4 had a low toxicity to L929 and HeLa cells in the absence of light. However, THPP-(PNIPAM-b-PMAGA)4 showed a high toxicity with HeLa cells under light irradiation which could be used as a potential photosensitizer for photodynamic therapy (PDT). In addition, THPP-(PNIPAM-b-PMAGA)4 showed specific a recognition function with Concanavalin A (Con A) to achieve active targeted drug delivery. This work provides a new approach for the development of tumor targeting and chemotherapy/PDT.

Synthesis and post-polymerization modification of star-shaped poly(ethylene glycol)-block-polydehydroalanine block copolymers: a versatile template for designing multifunctional polymers

We present the synthesis and solution properties of multifunctional star-shaped graft block copolymers via post-polymerization modification.

Dual-Crosslinked Degradable Elastomeric Networks With Self-Healing Properties: Bringing Multi(catechol) Star-Block Copolymers into Play

In the biomedical field, degradable chemically crosslinked elastomers are interesting materials for tissue engineering applications, since they present rubber-like mechanical properties matching those of soft tissues and are able to preserve their three-dimensional (3D) structure over degradation. Their use in biomedical applications requires surgical handling and implantation that can be a source of accidental damages responsible for the loss of properties. Therefore, their inability to be healed after damage or breaking can be a major drawback. In this work, biodegradable dual-crosslinked networks that exhibit fast and efficient self-healing properties at 37 °C are designed. Self-healable dual-crosslinked (chemically and physically) elastomeric networks are prepared by two methods. The first approach is based on the mix of hydrophobic poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) star-shaped copolymers functionalized with either catechol or methacrylate moieties. In the second approach, hydrophobic bifunctional PEG-PLA star-shaped copolymers with both catechol and methacrylate on their structure are used. In the two systems, the supramolecular network is responsible for the self-healing properties, thanks to the dynamic dissociation/reassociation of the numerous hydrogen bonds between the catechol groups, whereas the covalent network ensures mechanical properties similar to pure methacrylate networks. The self-healable materials display mechanical properties that are compatible with soft tissues and exhibit linear degradation because of the chemical cross-links. The performances of networks from mixed copolymers versus bifunctional copolymers are compared and demonstrate the superiority of the latter. The biocompatibility of the materials is also demonstrated, confirming the potential of these degradable and self-healable elastomeric networks to be used for the design of temporary medical devices.

Study of the phase-transition behavior of (AB)3 type star polystyrene-block-poly(n-butylacrylate) copolymers by the combination of rheology and SAXS

Abstract A series of three-armed star polystyrene-block-poly(n-butylacrylate) copolymers (PS-b-PBA)3 were synthesized to study the phase-transition behavior of the copolymers. The order-to-disorder transition temperature has been determined by oscillatory at different temperatures and dynamic temperature sweep at a fixed frequency. Moreover, the micro-phase separation in the block copolymers has been evaluated by time–temperature superposition, while the free volume and the active energy of the copolymers have been calculated. Interestingly, active energy decreased with the increase in the molecular weight of the PBA components. To further determine the order-to-disorder transition temperature precisely, small angle X-ray scattering was performed at different temperatures. These results confirm that the chain mobility of the star-shaped copolymers is strongly dependent on the arm molecular weight of the star polymers, which will be beneficial for the processing and material preparation of the block copolymers.