Polycarbonate Backbone Research Articles

A fully biodegradable spherical nucleic acid nanoplatform for self-codelivery of doxorubicin and miR122 for innate and adaptive immunity activation

Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa30-DOX-miR122 that can self-assemble into stabilized SNA. Besides the desired biodegradability, another notable merit of this nanoplatform is the use of miR122 not only for gene therapy but also for enhanced innate immune response. Together with the ICD-triggering effect of DOX, PBis-Mpa30-DOX-miR122 SNA-mediated DOX and miR122 codelivery leads to synergistic immunogenicity enhancement, resulting in tumor growth inhibition value (TGI) of 98.1 % significantly higher than those of the groups treated with only drug or gene in a Hepa1-6-tumor-bearing mice model. Overall, this study develops a useful strategy toward biodegradable SNA construction, and presents a drug and gene-based self-codelivery SNA with synergistic immunogenicity enhancement for efficient HCC therapy. Statement of significanceFacile construction of a fully biodegradable SNA nanoplatform is useful for in vivo applications but remains relatively unexplored likely due to the synthetic challenge. We report herein construction of a polycarbonate-based SNA nanoplatform for co-delivering a chemotherapeutic drug, DOX, and a human liver-specific miR-122 for synergistic HCC treatment. In addition to the desired biodegradability properties, this SNA nanoplatform integrates DOX-triggered ICD and miR-122-enhanced innate immunity for simultaneously activating adaptive and innate immunities, which leads to potent antitumor efficiency with a TGI value of 98.1 % in a Hepa1-6-tumor-bearing mice model.

Flexible Polycarbonate and Copoly(Imide-Carbonate)s-Based Frequency Selective Surface for Electromagnetic Shielding Application

Optically transparent polycarbonates (PCs) and Copoly(Imide-Carbonate)s (Co-PICs) were synthesized by the melt polycondenzation method. Rigid (imide) and flexible (-O- and –C(CH3)2−) moieties were incorporated in the structure of bisimide diol comonomer using 4-aminophenol and 4,4′-(4,4′-isopropylidenediphenoxy) bis(phthalic anhydride). The structural properties of synthesized comonomers and polymers were confirmed by 1H, 13C-NMR and FT-IR spectra. Thermal properties of polycarbonates and copolycarbonates were examined using DSC and TG analysis. Thermal properties (glass transition Tg and thermal decomposition (Td) temperature) of copolymers were enhanced without sacrificing properties of BPA-based PC (high transparency, ductility, and processability) by the incorporation of active functional bisimide diol comonomer (5–10 mole %) in the polycarbonate backbone. Different sets of PCs and Co-PICs thin film substrates were prepared by the solvent casting method and used to design frequency selective surface. The proposed flexible FSS offers shielding of 20 dB at 8.8 GHz. In addition, the FSS offers polarization independent operation with its symmetrical unit cell geometry.

A Biodegradable, Polymer-Supported Oxygen Atom Transfer Reagent.

Biodegradable polymers are desirable to mitigate the environmental impact of plastic waste in the environment. Over the past several decades, the development of organocatalytic ring-opening polymerization (OROP) has made the synthesis of many new types of biodegradable polymers possible. In this research article, the first example of an oxygen atom transfer reagent pendant on a biodegradable polymer backbone is reported. The monomers for the polycarbonate backbone are sourced from the biodegradable 2,2-bis(hydroxymethyl) propionic acid molecule, and an iodoaryl group is installed pendant to the cyclic monomer for post-polymerization modification into an iodosylaryl oxygen atom transfer reagent. The key I-O bond is characterized by XPS spectroscopy, and a test reaction to triphenylphosphine demonstrates the ability of the polymer to engage in an oxygen atom transfer reaction with a substrate.

Photothermally responsive smart elastomer composites based on aliphatic polycarbonate backbone for biomedical applications

Despite self-healing elastomers can autonomously heal physical damage of the interface of materials to reduce maintenance costs, utilization of self-healing ability and shape memory as sutures to promote wound healing has not been reported. Herein, novel photothermally responsive elastomer composites based on aliphatic polycarbonate and azobenzene units are reported, which exhibit highly efficient self-healing, controllable mechanical properties and excellent shape memory. Notably, the elastomer composites possess a unique, rapid light-responsive self-healing ability within only 5 min. The shape recovery time showed that the elastomer composites could completely recover to their original shape after 19.33 ± 0.29 s. The cell line studies and subsequent imaging indicate that the composites with good biocompatibility are superior biomaterials used in the biomedical arena. Spiral-like stent also displays fast response at 37 °C, finishing excellent self-expansion within only 10 s. In vivo experiments on injured wounds of rats demonstrate that the obtained composites as a self-tightening suture in keyhole surgery has the potential of excellent self-healing knotting ability and shape memory effect. The obtained self-tightening suture can quickly restore a programmed shape at physiological temperature, thereby effectively closing the injured wound surface, and without forming any scars after healing, which will provide a new direction for the future biomedical field.

Generation of microplastic particles during degradation of polycarbonate films in various aqueous media and their characterization

A 250-day batch experiment was conducted to examine the generation of microplastic particles from degradation of polycarbonate films in 3 aqueous media of environmental relevance. The microplastic particles generated from the experiment were characterized by SEM/EDS and micro-FTIR analysis. Hydrolysis was responsible for the cleavage of carbon-oxygen bonds in the carbonate group of polycarbonate backbone and detachment of micro-sized plastic particles from the PC film surfaces. The deionized water treatment had the highest concentration of total organic carbon and the greatest number of microplastic particles among the three treatments. Either elevated acidity or the presence of hydroxyl radical did not enhance the hydrolytic degradation of the PC films and generation of microplastic particles though hydroxyl radical caused oxidative degradation of polycarbonate by attacking the organic group but not the carbonate group. Bisphenol A was not detected in any of the treatments. The microplastic particles generated from the current experiment were highly irregular, which may have different physicochemical and toxic behaviours from the spheric synthetic ones that were frequently used in toxicity experiments.

Polycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window

Stimuli-sensitive nanomaterials with cooperative response are capable of converting subtle and gradual biological variations into robust outputs to improve the precision of diagnostic or therapeutic outcomes. In this study, we report the design, synthesis and characterization of a series of degradable ultra-pH sensitive (dUPS) polymers that amplify small acidic pH changes to efficacious therapeutic outputs. A hydrolytically active polycarbonate backbone is used to construct the polymer with pH-dependent degradation kinetics. One dUPS polymer, PSC7A, can achieve activation of the stimulator of interferon genes and antigen delivery upon endosomal pH activation, leading to T cell-mediated antitumor immunity. While a non-degradable UPS polymer induces granulomatous inflammation that persists over months at the injection site, degradable PSC7A primes a transient acute inflammatory response followed by polymer degradation and complete tissue healing. The improved therapeutic window of the dUPS polymers opens up opportunities in pH-targeted drug and protein therapy.

Sequence structure control of CO<sub>2</sub>-based copolymer and the relationship between structure and properties

<p indent=0mm>Carbon dioxide-based (CO₂-based) copolymer is an attractive environment-friendly material with excellent biodegradability and using non-toxic, abundant and cheap carbon dioxide gas as one of its raw materials. Since CO₂ is generated as a waste gas in many economic activities leading to global warming, chemical fixation of CO₂ can be a developing and effective mean to reduce evironmental and energy pressures. Among all the CO₂-based copolymers, the aliphatic polycarbonates obtained by the copolymerization of CO₂ and epoxides are the most widely studied materials due to their excellent biocompatity, transparency as well as water and oxygen barrier properties, especially poly(propylene carbonate)(PPC). However, undesirable thermal and mechanical properties limit their practical applications. For examples, PPC has a low <italic>T</italic>_g (35–40°C) close to room temperature, which is easy to bond into blocks during long-term storage and transportation after granulation, leading to the difficulty in subsequent processing. Much efforts have been devoted to tailor the structures of CO₂-based polycarbonates to obtain desirable peoperties profile. A feasible approach is to control the configurations of synthesized polycarbonates, which can greatly improve the thermal peoperties. Another effective way is to inrtoduce a third monomer into the CO₂/epoxides copolymerization to endow copolymers with tunable properties by easily changing the monomers and controlling polymer units. Herein, this article summarizes the methods for controlling the sequence structure of CO₂-based copolymers. Four kinds of CO₂-based copolymers are included: (1) Fully alternating polycarbonates with <italic>regio</italic>- and <italic>stereo</italic>-chemistry configurations. In this part, the efforts on the stereochemistry control of polycarbonates are highlighted and the crystallinity of polycarbonates are emphatically introduced. Isotactic polycarbonates have the higher glass transition temperature than the amorphous one and some of them are crystalline. Even though no cystallinity can be observed in isotactic PPC, the <italic>T</italic>_g was 35–40°C higher than the atactic one. (2) Terpolymers prepared from the copolymerization of CO₂ with different epoxides are introduced. Since the activity of different epoxides copolymerized with CO₂ varied greatly, especially the electron-withdrawing and electron-donating epoxides, the control on the compositions and connetions of CO₂/different epoxides terpolymers is a big challenge. Highly effective metal-based catalysts were designed to sucessfully synthesize defined random terpolymers. Moreover, block polycarbonates can only be synthesized by subsequent monomer additions which requires the completely removal or consumtion of the first monomer. CO₂-besed polycarbonates with high added value are desirable today. Hence, the efforts on the post-functionalization of polycarbonates are also highlighted. (3) Terpolymers of CO₂, epoxide and cyclic anhydride. The difference in the rates of CO₂/epoxides and cyclic anhydrides/epoxides copolymerization determines the microstructure of CO₂/epoxides/cyclic anhydrides terpolymers. Therefore, copolymers with random/gradient or block structures can be easily prepared by choosing the right catalysts. Note that, some attempts to improve copolymers’ properties by introducing the crosslinked sturctures were also successful. (4) Terpolymers of CO₂, epoxide and cyclic ester. Random poly(ester-carbonate)s can be generated via one-pot/one-step strategy by using heterogenous catalysts. However, synthesis of block CO₂/epoxides/cyclic esters terpolymers usually requires multi-step operations. The good news that one-pot chemical selective polymerization of mixed monomers can be fufilled by designing the catalysts, which can tune the sequence structures of copolymers by a switch. Multiblock terpolymers are also presented. Finally, the thermal, thermal, mechanical and degradation properties of CO₂-based terpolymers are reviewed in each part to varify the relationships between structures and properties. In a summary, inserting a third monomer into the polycarbonate backbone through terpolymerization is a robust tool to tune polymers’ performances. The development directions of CO₂-based copolymers are prospected in the end.

Guanidinylated Amphiphilic Polycarbonates with Enhanced Antimicrobial Activity by Extending the Length of the Spacer Arm and Micelle Self-Assembly.

Nine guanidinylated amphiphilic polycarbonates are rationally designed and synthesized. Each polymer has the same biodegradable backbone but different side groups. The influence of the hydrophobic/hydrophilic effect on antimicrobial activities and cytotoxicity is systematically investigated. The results verify that tuning the length of the spacer arm between the cationic guanidine group and the polycarbonate backbone is an efficient design strategy to alter the hydrophobic/hydrophilic balance without changing the cationic charge density. A spacer arm of six methylene units (CH2 )6 shows the best antimicrobial activity (minimum inhibitory concentration, MIC = 40 µg mL-1 against Escherichia coli, MIC = 20 µg mL-1 against Staphylococcus aureus, MIC = 40 µg mL-1 against Candida albicans) with low hemolytic activity (HC50 > 2560 µg mL-1 ). Furthermore, the guanidinylated polycarbonates exhibit the ability to self-assemble and present micelle-like nanostructure due to their intrinsic amphiphilic macromolecular structure. Transmission electron microscopy and dynamic light scattering measurements confirm polymer micelle formation in aqueous solution with sizes ranging from 82 to 288 nm.

High Conductivity, Lithium Ion Conducting Polymer Electrolyte Based on Hydrocarbon Backbone with Pendent Carbonate

Solid polymer electrolytes (sPE) offer a pathway for safer, less flammable lithium batteries. However, developing a polymer that provides high Li+ mobility as well electrochemical stability remains a challenge, because ion conductive functional units in the polymer main-chain (e.g., polycarbonate and polyether) usually suffer from poor electrochemical stability at high and low potentials. Herein, an sPE with pendent carbonate on a hydrocarbon backbone has been designed and synthesized to overcome conductivity and electrochemical stability problems. This pendant polycarbonate is different from conventional polycarbonate electrolytes because the carbonate moiety is in the sidechain, which mitigates polycarbonate backbone stability problems while still providing high ionic conductivity when used with a plasticizer. Conductivity as high as 1.1 mS cm−1 at 22 °C was obtained. Stable lithium metal plating and stripping using the sPE was observed for 1,200 h and electrochemical stability up to 4.6 V vs Li+/Li has been demonstrated. The low interfacial resistance (<160 ohm∙cm2 at 22 °C) and reasonable ionic conductivity have enabled acceptable cycling performance in a Li-LiFePO4 battery at 0.98 mA cm−2 for 2,300 cycles.

Bio-Based Thermo-Reversible Aliphatic Polycarbonate Network.

Aliphatic polycarbonates represent an important class of materials with notable applications in the biomedical field. In this work, low Tg furan-functionalized bio-based aliphatic polycarbonates were cross-linked thanks to the Diels–Alder (DA) reaction with a bis-maleimide as the cross-linking agent. The thermo-reversible DA reaction allowed for the preparation of reversible cross-linked polycarbonate materials with tuneable properties as a function of the pendent furan content that was grafted on the polycarbonate backbone. The possibility to decrosslink the network around 70 °C could be an advantage for biomedical applications, despite the rather poor thermal stability of the furan-functionalized cross-linked polycarbonates.

Preparation of fluorophore-tagged polymeric drug delivery vehicles with multiple biological stimuli-triggered drug release.

In the field of drug delivery, the controlled release of drugs is continuously one of the highly prioritized research domains. Stimuli-responsive polymers are being investigated as drug delivery vehicles that modulate pharmaceutical effect via tumor specific mechanisms. In this work, a biocompatible graft copolymer (denoted as PSNC-g-mPEG/TPE) was constructed, which comprised a triple-responsive polycarbonate backbone coupled with fluorescent TPE and hydrophilic methoxypoly(ethylene glycol) (mPEG) segments. This multifunctional amphiphilic copolymer was able to self-assemble in aqueous solutions and acted as a drug delivery vehicle that releases cargo in response to multiple biological stimuli (ROS, pH and enzymes). And the results of confocal laser scanning microscopy (CLSM) suggested that these micelles could be rapidly internalized by cells and achieve more effective drug release in cancer cells. Furthermore, the cytotoxicity assays proved the safety of this material. It is anticipated that this strategy has enormous potential in constructing novel anticancer therapeutics.

Biomechanical Behaviour and Biocompatibility of Ureidopyrimidinone-Polycarbonate Electrospun and Polypropylene Meshes in a Hernia Repair in Rabbits.

Although mesh use has significantly improved the outcomes of hernia and pelvic organ prolapse repair, long-term recurrence rates remain unacceptably high. We aim to determine the in vivo degradation and functional outcome of reconstructed abdominal wall defects, using slowly degradable electrospun ureidopyrimidinone moieties incorporated into a polycarbonate backbone (UPy-PC) implant compared to an ultra-lightweight polypropylene (PP) textile mesh with high pore stability. Twenty four New-Zealand rabbits were implanted with UPy-PC or PP to either reinforce a primary fascial defect repair or to cover (referred to as gap bridging) a full-thickness abdominal wall defect. Explants were harvested at 30, 90 and 180 days. The primary outcome measure was uniaxial tensiometry. Secondary outcomes were the recurrence of herniation, morphometry for musculofascial tissue characteristics, inflammatory response and neovascularization. PP explants compromised physiological abdominal wall compliance from 90 days onwards and UPy-PC from 180 days. UPy-PC meshes induced a more vigorous inflammatory response than PP at all time points. We observed progressively more signs of muscle atrophy and intramuscular fatty infiltration in the entire explant area for both mesh types. UPy-PC implants are replaced by a connective tissue stiff enough to prevent abdominal wall herniation in two-thirds of the gap-bridged full-thickness abdominal wall defects. However, in one-third there was sub-clinical herniation. The novel electrospun material did slightly better than the textile PP yet outcomes were still suboptimal. Further research should investigate what drives muscular atrophy, and whether novel polymers would eventually generate a physiological neotissue and can prevent failure and/or avoid collateral damage.

Preparation of Light‐Responsive Aliphatic Polycarbonate via Versatile Polycondensation for Controlled Degradation

AbstractStarting from (2,2,5‐trimethyl‐1,3‐dioxan‐5‐yl)methanamine with light‐responsive 4,5‐dimethoxy‐2‐nitrobenzyl protecting groups, a variety of light‐responsive copolycarbonates (LrPCs) are synthesized by a general two‐step polycondensation using lithium acetylacetonate (LiAcac) as catalyst. UV/Vis, 1H nuclear magnetic resonance (NMR), and size exclusion chromatography (SEC) confirm the rapid decomposition of these polymers in response to irradiation with UV light. Stable and monodisperse nanoparticles with hydrodynamic diameters of 100 nm, formulated from 25% LrPC and 75% poly(lactic‐co‐glycolic acid) (PLGA), undergo rapid disruption upon triggering with UV light, while standard PLGA nanoparticles remain stable. Moreover, differing from the ring‐opening polymerization (ROP) of trimethylene carbonate‐based monomers, direct polycondensation of 1,3‐propanediol‐based monomers with pendent functional groups and other diols will enable the introduction of various properties into the polycarbonate backbone, and expand the family of biodegradable synthetic polymers for potential biomedical applications.

Functional polycarbonates for improved adhesion to carbon fibre

In order to improve the fibre-matrix interaction in carbon fibre reinforced composites the polycarbonate (PC) matrix polymer was modified by the introduction of ethyl-3,5-dihydroxybenzoate as reactive sequences in the polycarbonate backbone. This promising strategy can be considered as an alternative approach to the modification of the carbon fibre surface to control and tailor the adhesion between carbon fibres and polymer matrix. The modification of the polycarbonate demonstrated improved adhesion to carbon fibre in pressed films, which was observed with microscopy-ATR-FTIR and SEM when compared to unmodified polycarbonate. Single fibre pull-out testing subsequently confirmed the improved adhesion, demonstrating higher interfacial shear strenght for the functionalized polycarbonate.

Simple and Efficient Approach toward Photosensitive Biobased Aliphatic Polycarbonate Materials.

Fatty acids were used as precursors for the synthesis of photosensitive polycarbonate materials. In order to avoid multistep reactions, a simple and straightforward methodology toward the synthesis of photosensitive monomers has been developed. Hence, a fatty acid-based cyclic carbonate bearing an unsaturation was synthesized and subsequently polymerized in a controlled manner (Đ = 1.07) by organo-catalyzed ring-opening polymerization (ROP). A thio-cinnamate derivative was then readily synthesized via a one-pot reaction and grafted onto the polycarbonate backbone by thiol-ene reaction. The content of photoresponsive cinnamoyl moiety grafted on the polycarbonate was tunable with the reaction time. Such functionalized polycarbonates could be crosslinked (by UV irradiation at 365 nm) and partially decrosslinked (irradiated at 254 nm) and exhibit versatile properties ranging from rather tough materials to elastomeric networks with respect to the content of the photosensitive cinnamoyl moiety grafted on the polymer.

Organocatalytic Synthesis and Evaluation of Polycarbonate Pendant Polymer:β-Cyclodextrin-Based Nucleic Acid Delivery Vectors

A family of mPEG-b-polycarbonate (mPEG-PC) diblock pendant polymers were synthesized from trimethylene carbonate and other cyclic carbonate monomers bearing hydrophobic guest ligands via organocatalytic ring-opening polymerization using 1,4,5-triazabicyclo[4.4.0]dec-5-ene catalyst or 1,8-diazabicyclo[5.4.0]undec-7-ene/thiourea cocatalyst. Diblock copolymers composed of a methoxypoly(ethylene oxide) (mPEG) block and a polycarbonate block containing either homopolymer or mixed polycarbonates (PC) were prepared by homopolymerization or copolymerization of the cyclic carbonate monomers in the presence of mPEG2000 or mPEG5000 initiator to give materials having a tunable pendant group density along the polycarbonate backbone. Polycarbonate blocks targeting the 2.4–10 kDa range were prepared with good molecular weight control and modest polydispersities (averaging ∼1.3). Complexation of plasmid DNA with β-cyclodextrin–polyethylenimine2.5 kDa produced nanoparticle cores that were then coated with the mPEG–PC dibl...

Convergent Approach to Boronic Acid Functionalized Polycarbonates: Accessing New Dynamic Material Platforms.

Polycarbonates are routinely utilized for diverse medicinal applications and are highly efficacious scaffolds for drug delivery and antimicrobial treatments. In order to provide for robust, dynamic platforms for biomedical applications, we have developed new routes for the incorporation of boronic acids into the polycarbonate backbone. These routes take advantage of straightforward postsynthesis modification of established polycarbonate backbones, enabling the preparation of a diverse array of boronic acid functionalized polycarbonates from readily accessible polycarbonates. In particular, this approach circumvents the need for de novo monomer synthesis, functional group incompatibilities, and deprotection steps that often limit other methods. This strategy has been demonstrated using a broad array of unprotected boronic acids to produce both neutral and cationic boronic acid functionalized polycarbonates.

New side chain cholesterol-functionalised aliphatic polycarbonate copolymer: synthesis and phase behaviour

ABSTRACTA new side cholesterol-functionalised liquid crystal (LC) copolymer based on aliphatic polycarbonate backbone was synthesised. The chemical structures of the block copolymers obtained in this study were characterised with Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1H NMR) spectra. Their thermal stability and phase behaviours were investigated with thermogravimetric analysis (TGA) measurements, differential scanning calorimetry, and polarising optical microscopy. The molecular organisation in the mesophase was studied by temperature-dependent X-ray diffraction (XRD). As a result, the block copolymer bearing side cholesteryl groups showed a glass transition at 15.8°C and a smectic A (SmA) to isotropic phase transition at 151.3°C on heating cycle. XRD indicated that the block LC copolymer showed an interdigitated molecular arrangement of the mesogenic units within the smectic layers. This partial bilayer structure was similar to the SmA phase formed by polar mesogens.

New amphiphilic polycarbonates with side functionalized cholesteryl groups as biomesogenic units: synthesis, structure and liquid crystal behavior

In this study, a series of new side cholesterol-functionalized amphipathic copolymers based on an aliphatic polycarbonate backbone were synthesized and characterized.

Cyclic Graft Copolymer Unimolecular Micelles: Effects of Cyclization on Particle Morphology and Thermoresponsive Behavior.

The synthesis of cyclic amphiphilic graft copolymers with a hydrophobic polycarbonate backbone and hydrophilic poly(N-acryloylmorpholine) (PNAM) side arms via a combination of ring-opening polymerization (ROP), cyclization via copper-catalyzed azide–alkyne cycloaddition (CuAAC), and reversible addition–fragmentation chain transfer (RAFT) polymerization is reported. The ability of these cyclic graft copolymers to form unimolecular micelles in water is explored using a combination of light scattering, small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryoTEM) analyses, where particle size was found to increase with increasing PNAM arm length. Further analysis revealed differences in the solution conformations, loading capabilities, and morphologies of the cyclic graft copolymers in comparison to equivalent linear graft copolymer unimolecular micelle analogues. Furthermore, the cyclic and linear graft copolymers were found to exhibit significantly different cloud point temperatures. This study highlights how subtle changes in polymer architecture (linear graft copolymer versus cyclic graft copolymer) can dramatically influence a polymer’s nanostructure and its properties.