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•Bifunctional PEG endows SF aerogel with flexibility and structural stability.•cPEG promotes pyrrole binding onto SF scaffold and PPy deposition.•Flexible and conductive SF aerogel ...exhibits potential as a pressure sensor.
Silk fibroin (SF) has excellent biocompatibility and can be regenerated to obtain diverse materials. However, high brittleness and poor elasticity limit its applications in flexible devices, mainly due to high amounts of β-sheet structures in SF. Herein, a flexible SF aerogel is prepared by coupling polyethylene glycol (PEG) containing double-carboxyl end group with fibroin chains. This is followed by ammonium persulfate (APS)-initiated deposition of polypyrrole (PPy) units onto the scaffold. The bifunctional PEG not only improves the elasticity of SF aerogel, but it also promotes the accumulation of pyrrole cations on the fibroin surface and guides the formation of PPy. Meanwhile, PPy distributed in the SF matrix forms an electrically conductive pathway with an encouraging static conductivity, which is responsive to environmental humidity and external pressure. The sensitivity of the prepared SF-based conductive aerogel as a pressure sensor is much better than those reported in literature. Meanwhile, the stress and resistance show good synchronization during cyclic compressions. The present work provides a promising alternative for the fabrication of fibroin-based flexible and conductive aerogels as highly sensitive pressure sensors.
Dissipative self-assembly is common in biological systems, where it serves to maintain a far-from-equilibrium functional state through fuel consumption. Synthetic dissipative systems have been ...prepared that can mimic some of the properties of biological systems, but they often show poor mechanical performance. Here, we report a shear-induced transient hydrogel that is highly stretchable. The system is constructed by adding Cu(II) into the aqueous solution of a pseudopolyrotaxane, which is itself formed by threading molecular tubes on polyethylene glycol chains. Vigorous shaking transforms the solution into a gel, which gradually relaxes back to the sol state over time. This cycle can be repeated at least five times. A mechanism is proposed that relies on a shear-induced transition from intrachain to interchain coordination and subsequent thermal relaxation. The far-from-equilibrium hydrogel is highly stretchable, which is probably due to 'frictional' sliding of the molecular tubes on the polyethylene glycol chains. On shaking, the hydrogel undergoes fast self-healing.
While poly(ethylene glycol) (PEG) hydrogels are generally regarded as biologically inert blank slates, concerns over PEG immunogenicity are growing, and the implications for tissue engineering are ...unknown. Here, we investigate these implications by immunizing mice against PEG to stimulate anti-PEG antibody production and evaluating bone defect regeneration after treatment with bone morphogenetic protein-2-loaded PEG hydrogels. Quantitative analysis reveals that PEG sensitization increases bone formation compared to naive controls, whereas histological analysis shows that PEG sensitization induces an abnormally porous bone morphology at the defect site, particularly in males. Furthermore, immune cell recruitment is higher in PEG-sensitized mice administered the PEG-based treatment than their naive counterparts. Interestingly, naive controls that were administered a PEG-based treatment also develop anti-PEG antibodies. Sex differences in bone formation and immune cell recruitment are also apparent. Overall, these findings indicate that anti-PEG immune responses can impact tissue engineering efficacy and highlight the need for further investigation.
Reactant solubility, which dictates achievable concentrations, and the stability of reaction intermediates (excited states), solvents modulate the potential energy landscape and influence reaction ...rates. Consequently, solvent selection is pivotal in optimizing process productivity, economic feasibility, and environmental footprint. At present, organic synthesis pivots around the idea of sustainability. In particular, PEG‐400, a popular solvent and phase transfer catalyst, is considered greener as it can be reused several times without significant loss in its catalytic activity, which checks the box regarding sustainability. This review highlights the emerging potential of Polyethylene Glycol 400 (PEG‐400) as a dual‐threat agent in sustainable organic synthesis. We explore its efficacy as a catalyst, promoting various reactions under mild conditions and often eliminating the need for traditional metal catalysts. Additionally, PEG‐400's role as a green solvent is addressed, emphasizing its biodegradability, low toxicity, and ability to facilitate reactions without hazardous Volatile Organic Compounds (VOCs). The review examines recent research on PEG‐400 mediated reactions, showcasing its effectiveness in diverse transformations, thus exploring the potential of PEG 400 as a facilitator for heterocycle synthesis in both multicomponent reactions and stepwise approaches. It identifies exciting research directions that promise to expand the boundaries of polymer‐based solvents in heterocyclic chemistry.
•For the first time, hollow WS2 spheres with large surface area are used for drug delivery.•The surface of hollow WS2 was modified and chemotherapy drug was loaded.•The controlled release of the ...chemotherapy drug was achieved by Near-Infrared irradiation.
For the first time, hollow structured WS2 particles with large surface area are used for drug delivery application, because a large specific surface area is a strong demand for drug delivery carriers for the maximum drug loading. The synthesis was followed by surface modification and drug loading. The composite was finally sealed with the phase change material to prevent the drug leakage before the composite reaching the tumor sites. The polyethylene glycol (PEG) and doxorubicin (DOX) loading were confirmed by Fourier-Transform Infrared (FT-IR), UV-Vis spectroscopy, and thermogravimetric analysis, and the specific surface area was determined with BET method. The DOX drug release was studied at various environment temperature under 808 nm laser irradiation. Finally, the biocompatibility and cytotoxicity of the drug delivery system were studied with liver tumor cells.
All known triterpenes are generated by triterpene synthases (TrTSs) from squalene or oxidosqualene
. This approach is fundamentally different from the biosynthesis of short-chain (C
-C
) terpenes ...that are formed from polyisoprenyl diphosphates
. In this study, two fungal chimeric class I TrTSs, Talaromyces verruculosus talaropentaene synthase (TvTS) and Macrophomina phaseolina macrophomene synthase (MpMS), were characterized. Both enzymes use dimethylallyl diphosphate and isopentenyl diphosphate or hexaprenyl diphosphate as substrates, representing the first examples, to our knowledge, of non-squalene-dependent triterpene biosynthesis. The cyclization mechanisms of TvTS and MpMS and the absolute configurations of their products were investigated in isotopic labelling experiments. Structural analyses of the terpene cyclase domain of TvTS and full-length MpMS provide detailed insights into their catalytic mechanisms. An AlphaFold2-based screening platform was developed to mine a third TrTS, Colletotrichum gloeosporioides colleterpenol synthase (CgCS). Our findings identify a new enzymatic mechanism for the biosynthesis of triterpenes and enhance understanding of terpene biosynthesis in nature.
Benefiting from their inherent localized and controlled release properties, hydrogels are ideal delivery systems for therapeutic drugs or nanoparticles. In particular, applications of hydrogels for ...the delivery and release of photoresponsive drugs or nanoparticles are receiving increasing attention. However, the effect of the hydrogel matrix on the fluorescence emission and singlet oxygen generation efficiency of the embedded photosensitizers (PSs) has not been clarified. Herein, meso-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP) as a water-soluble PS was encapsulated into an injectable hydrogel formed by glycol chitosan and dibenzaldehyde-terminated telechelic poly(ethylene glycol). Compared to free TMPyP solution, the TMPyP encapsulated in the hydrogel exhibits three distinct advantages: (1) more singlet oxygen was generated under the same laser irradiation condition; (2) much longer tumor retention was observed due to the low fluidity of the hydrogel; and (3) the fluorescence intensity of TMPyP was significantly enhanced in the hydrogel due to its decreased self-quenching effect. These excellent characteristics lead to remarkable anticancer efficacy and superior fluorescence emission property of the TMPyP–hydrogel system, promoting the development of imaging-guided photodynamic therapy.
Summary Background Phenylketonuria is an inherited disease caused by impaired activity of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, leading to accumulation of ...phenylalanine and subsequent neurocognitive dysfunction. Phenylalanine ammonia lyase is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. We aimed to assess the safety, tolerability, pharmacokinetic characteristics, and efficacy of recombinant Anabaena variabilis phenylalanine ammonia lyase (produced in Escherichia coli ) conjugated with polyethylene glycol (rAvPAL-PEG) in reducing phenylalanine concentrations in adult patients with phenylketonuria. Methods In this open-label, phase 1, multicentre trial, single subcutaneous injections of rAvPAL-PEG were given in escalating doses (0·001, 0·003, 0·010, 0·030, and 0·100 mg/kg) to adults with phenylketonuria. Participants aged 18 years or older with blood phenylalanine concentrations of 600 μmol/L or higher were recruited from among patients attending metabolic disease clinics in the USA. The primary endpoints were safety and tolerability of rAvPAL-PEG. Secondary endpoints were the pharmacokinetic characteristics of the drug and its effect on concentrations of phenylalanine. Participants and investigators were not masked to assigned dose group. This study is registered with ClinicalTrials.gov , number NCT00925054. Findings 25 participants were recruited from seven centres between May 6, 2008, and April 15, 2009, with five participants assigned to each escalating dose group. All participants were included in the safety population. The most frequently reported adverse events were injection-site reactions and dizziness, which were self-limited and without sequelae. Two participants had serious adverse reactions to intramuscular medroxyprogesterone acetate, a drug that contains polyethylene glycol as an excipient. Three of five participants given the highest dose of rAvPAL-PEG (0·100 mg/kg) developed a generalised skin rash. By the end of the study, all participants had developed antibodies against polyethylene glycol, and some against phenylalanine ammonia lyase as well. Drug concentrations peaked about 89–106 h after administration of the highest dose. Treatment seemed to be effective at reducing blood phenylalanine in all five participants who received the highest dose (mean reduction of 54·2% from baseline), with a nadir about 6 days after injection and an inverse correlation between drug and phenylalanine concentrations in plasma. Phenylalanine returned to near-baseline concentrations about 21 days after the injection. Interpretation Subcutaneous administration of rAvPAL-PEG in a single dose of up to 0·100 mg/kg was fairly safe and well tolerated in adult patients with phenylketonuria. At the highest dose tested, rAvPAL-PEG reduced blood phenylalanine concentrations. In view of the development of antibodies against polyethylene glycol (and in some cases against phenylalanine ammonia lyase), future studies are needed to assess the effect of repeat dosing. Funding BioMarin Pharmaceutical.
A recent trend has emerged that involves myocardial injection of biomaterials, containing cells or acellular, following myocardial infarction (MI) to influence the remodeling response through both ...biological and mechanical effects. Despite the number of different materials injected in these approaches, there has been little investigation into the importance of material properties on therapeutic outcomes. This work focuses on the investigation of injectable hyaluronic acid (MeHA) hydrogels that have tunable mechanics and gelation behavior. Specifically, two MeHA formulations that exhibit similar degradation and tissue distribution upon injection but have differential moduli (∼8 versus ∼43 kPa) were injected into a clinically relevant ovine MI model to evaluate the associated salutary effect of intramyocardial hydrogel injection on the remodeling response based on hydrogel mechanics. Treatment with both hydrogels significantly increased the wall thickness in the apex and basilar infarct regions compared with the control infarct. However, only the higher-modulus (MeHA High) treatment group had a statistically smaller infarct area compared with the control infarct group. Moreover, reductions in normalized end-diastolic and end-systolic volumes were observed for the MeHA High group. This group also tended to have better functional outcomes (cardiac output and ejection fraction) than the low-modulus (MeHA Low) and control infarct groups. This study provides fundamental information that can be used in the rational design of therapeutic materials for treatment of MI.
Simplifying synthesis and administration process, improving photothermal agents’ accumulation in tumors, and ensuring excellent biocompatibility and biodegradability are keys to promoting the ...clinical application of photothermal therapy. However, current photothermal agents have great difficulties in meeting the requirements of clinic drugs from synthesis to administration. Herein, we reported the in situ formation of a Ca2+/Mg2+ stimuli-responsive ICG–alginate hydrogel in vivo for localized tumor photothermal therapy. An ICG–alginate hydrogel can form by the simple introduction of Ca2+/Mg2+ into ICG–alginate solution in vitro, and the widely distributed divalent cations in organization in vivo enabled the in situ fabrication of the ICG–alginate hydrogel without the leakage of any agents by simple injection of ICG–alginate solution into the body of mice. The as-prepared ICG–alginate hydrogel not only owns good photothermal therapy efficacy and excellent biocompatibility but also exhibits strong ICG fixation ability, greatly benefiting the high photothermal agents’ accumulation and minimizing the potential side effects induced by the diffusion of ICG to surrounding tissues. The in situ-fabricated ICG–alginate hydrogel was applied successfully in highly efficient PTT in vivo without obvious side effects. Besides, the precursor of the hydrogel, ICG and alginate, can be stored in a stable solid form, and only simple mixing and noninvasive injection are needed to achieve PTT in vivo. The proposed in situ gelation strategy using biocompatible components lays down a simple and mild way for the fabrication of high-performance PTT agents with the superiors in the aspects of synthesis, storage, transportation, and clinic administration.
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