Glycol Derivatives Research Articles

Development of ROS-sensitive capofungin hydrogel by crosslinking chitosan with four-arm polyethylene glycol derivative for treatment of vulvovaginal candidiasis

Both exogenous and endogenous reactive oxygen species (ROS) in vulvovaginal candidiasis (VVC) play pivotal roles in promoting the hyphal formation of Candida albicans (CA), which suggests that clearing ROS could inhibit CA hyphae formation. A ROS-sensitive hydrogel (CAS@4Arm-PB/CS) was formulated by using a novel four-arm polyethylene glycol (4Arm-PEG) derivative (4Arm-PB) as a crosslinking agent, chitosan (CS) as the hydrogel matrix, and caspofungin (CAS) as the antifungal drug against CA. The ROS-sensitivity, disintegration mechanism, crosslinking action, swelling degree, microstructure, modulus, and rheological properties of 4Arm-PB were characterized. According to the results, 5.0 % 4Arm-PB could quickly and efficiently cross-link 0.5 mg/mL of CS. The ROS-sensitivity of 4Arm-PB was 10–50 μM, indicating a strong ROS sensitivity. The in vitro and in vivo anti-CA results indicated that CAS@4Arm-PB/CS not only cleared endogenous and exogenous ROS and inhibited the formation of CA hyphae and biofilm but also contributed beneficially to the treatment of VVC mice caused by CA infection, implying a certain safety aspect and an in vivo applicability. This research introduces a novel functional crosslinking agent for CS hydrogel formulation, presenting a new avenue for hydrogel-based drug delivery systems and therapeutic strategies for VVC treatment.

Characterization of a Novel Monoclonal Antibody with High Affinity and Specificity against Aflatoxins: A Discovery from Rosetta Antibody-Ligand Computational Simulation.

Aflatoxin B1 (AFB1) accumulates in crops, where it poses a threat to human health. To detect AFB1, anti-AFB1 monoclonal antibodies have been developed and are widely used. While the sensitivity and specificity of these antibodies have been extensively studied, information regarding the atomic-level docking of AFB1 (and its derivatives) with these antibodies is limited. Such information is crucial for understanding the key interactions that are required for high affinity and specificity in aflatoxin binding. First, a 3D comparative model of anti-AFB1 antibody (Ab-4B5G6) was predicted from the sequence using RosettaAntibody. We then utilized RosettaLigand to dock AFB1 onto ten homology models, producing a total of 10,000 binding modes. Interestingly, the best-scoring mode predicted strong interactions involving four sites within the heavy chain: ALA33, ASN52, HIS95, and TRP99. Importantly, these strong binding interactions exclusively involve the variable domain of the heavy chain. The best-scoring mode with AFB1 was also obtained through AF multimer combined with RosettaLigand, and two interactions at TRP and HIS were consistent with those found by Rosetta antibody-ligand computational simulation. The role of tryptophan in π interactions in antibodies was confirmed through mutation experiments, and the resulting mutant (W99A) exhibited a >1000-fold reduction in binding affinity for AFB1 and analogs, indicating the effect of tryptophan on the stability of CDR-H3 region. Additionally, we evaluated the binding of two glycolic acid-derived molecular derivatives (with impaired hydrogen bonding potential), and these derivatives (AFB2-GA and AFG2-GA) demonstrated a very weak binding affinity for Ab-4B5G6. The heavy chain was successfully isolated, and its sensitivity and specificity were consistent with those of the intact antibody. The homology models of variable heavy (VH) single-domain antibodies were established by RosettaAntibody, and the docking analysis revealed the same residues, including Ala, His, and Trp. Compared to the potential binding mode of fragment variable (FV) region, the results from a model of VH indicated that there are seven models involved in hydrophobic interaction with TYR32, which is usually referred to as polar amino acid and has both hydrophobic and hydrophilic features depending on the circumstances. Our work encompasses the entire process of Rosetta antibody-ligand computational simulation, highlighting the significance of variable heavy domain structural design in enhancing molecular interactions.

An Injectable Hydrogel with Ultrahigh Burst Pressure and Innate Antibacterial Activity for Emergency Hemostasis and Wound Repair.

Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion, slow adhesion formation, cytotoxicity concerns, and lack of antibacterial properties. Herein, an injectable hydrogel (denoted as ES gel) with rapid, robust adhesive sealing and inherent antibacterial activity based on ε-polylysine and a poly(ethylene glycol) derivative is developed. The engineered hydrogel exhibits rapid gelation behavior, high mechanical strength, strong adhesion to various tissues, and can sustain an ultrahigh burst pressure of 450mmHg. It also presents excellent biocompatibility, biodegradability, antibacterial properties, and on-demand removability. Significantly improved hemostatic efficacy of ES gel compared to fibrin glue is demonstrated using various injury models in rats and rabbits. Remarkably, the adhesive hydrogel can effectively halt lethal non-compressible hemorrhages in visceral organs (liver, spleen, and heart) and femoral artery injury models in fully anticoagulated pigs. Furthermore, the hydrogel outperforms commercial products in sutureless wound closure and repair in the rat liver defect, skin incision, and infected full-thickness skin wound models. Overall, this study highlights the promising clinical applications of ES gel for managing uncontrolled hemorrhage, sutureless wound closure, and infected wound repair.

Fluorine-Free Single-Component Polyelectrolyte of Poly(ethylene glycol) Bearing Lithium Methanesulfonylsulfonimide Terminal Groups: Effect of Structural Variance on Ionic Conductivity

Fluorine-free single-component polyelectrolytes were developed via the hybridization of lithium methanesulfonylsulfonimide (LiMSSI) moieties to poly(ethylene glycol) (PEG) derivatives with different morphologies, and the relationship between the structure and its ionic conductivity was investigated. The PEG-LiMSSI derivatives with one, two, and three LiMSSI end groups were prepared via the concomitant Michael-type addition and lithiation of PEGs and N-methanesulfonylvinylsulfonimide. The ionic conductivity at 60 °C ranged from 1.8 × 10−7 to 2.0 × 10−4 S/cm. PEG-LiMSSI derivatives with one LiMSSI terminus and with two LiMSSI termini at both ends show higher ionic conductivity, that is as good as fluorine-free single-component polyelectrolytes, than that with two LiMSSI termini at one end and that with three LiMSSI termini.

Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration.

Stem cell-derived extracellular vesicles (EVs) show great potential for promoting bone tissue regeneration. However, normal EVs (Nor-EVs) have a limited ability to direct tissue-specific regeneration. Therefore, it is necessary to optimize the osteogenic capacity of EV-based systems for repairing extensive bone defects. Herein, we show that hydrogels loaded with osteoinductive dental pulp stem cell-derived EVs (Ost-EVs) enhanced bone tissue remodeling, resulting in a 2.23 ± 0.25-fold increase in the expression of bone morphogenetic protein 2 (BMP2) compared to the hydrogel control group. Moreover, Ost-EVs led to a higher expression of alkaline phosphatase (ALP) (1.88 ± 0.16 of Ost-EVs relative to Nor-EVs) and the formation of orange-red calcium nodules (1.38 ± 0.10 of Ost-EVs relative to Nor-EVs) in vitro. RNA sequencing revealed that Ost-EVs showed significantly high miR-1246 expression. An ideal hydrogel implant should also adhere to surrounding moist tissues. In this study, we were drawn to mussel-inspired adhesive modification, where the hydrogel carrier was crafted from hyaluronic acid (HA) and polyethylene glycol derivatives, showcasing impressive tissue adhesion, self-healing capabilities, and the ability to promote bone growth. The modified HA (mHA) hydrogel was also responsive to environmental stimuli, making it an effective carrier for delivering EVs. In an ectopic osteogenesis animal model, the Ost-EV/hydrogel system effectively alleviated inflammation, accelerated revascularization, and promoted tissue mineralization. We further used a rat femoral condyle defect model to evaluate the in situ osteogenic ability of the Ost-EVs/hydrogel system. Collectively, our results suggest that Ost-EVs combined with biomaterial-based hydrogels hold promising potential for treating bone defects.

A comparative transcriptomics analysis reveals ethylene glycol derivatives of squalene ameliorate excessive lipogenesis and inflammatory response in 3T3-L1 preadipocytes

Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives. Enrichment analyses of the transcriptional data showed that compared with SQ, its EG derivatives exerted different, in most cases desirable, biological responses. EG derivatives showed increased enrichment of mitochondrial functions, lipid and glucose metabolism, and inflammatory response. Mono-, di-, and tetra-SQ showed higher enrichment of the cellular component-ribosome. Histological staining showed EG derivatives prevented excessive lipid accumulation. Additionally, mitochondrial transcription factors showed upregulation in tetra-SQ-treated cells. Notably, EG derivatives showed better anti-inflammatory effects. Further, gene-disease association analysis predicted substantial improvement in the bioactivities of SQ derivatives in metabolic diseases. Cluster analyses revealed di- and tetra-SQ had more functional similarities than others, reflected in their scanning electron microscopy images; both di- and tetra-SQ self-organized into similar sizes and shapes of vesicles, subsequently improving their cation binding activities. Protein-protein interaction networks further revealed that cation binding activity might explain a major part, if not all, of the differences observed in functional analyses. Altogether, the addition of EG derivatives may improve the biological responses of SQ and thus may enhance its health-promoting potential.

Double cross-linked graphene oxide hydrogel for promoting healing of diabetic ulcers.

This study explores the synthesis and characterization of a novel double cross-linked hydrogel composed of polyvinyl alcohol (PVA), sodium alginate (SA), graphene oxide (GO), and glutathione (GSH), henceforth referred to as PVA/SA/GO/GSH. This innovative hydrogel system incorporates two distinct types of cross-linking networks and is meticulously engineered to exhibit sensitivity to high glucose and/or reactive oxygen species (ROS) environments. A sequential approach was adopted in the hydrogel formation. The initial phase involved the absorption of GSH onto GO, which was subsequently functionalized with boric acid and polyethylene glycol derivatives via a bio-orthogonal click reaction. This stage constituted the formation of the first chemically cross-linked network. Subsequently, freeze-thaw cycles were utilized to induce a secondary cross-linking process involving PVA and SA, thereby forming the second physically cross-linked network. The resultant PVA/SA/GO/GSH hydrogel retained the advantageous hydrogel properties such as superior water retention capacity and elasticity, and additionally exhibited the ability to responsively release GSH under changes in glucose concentration and/or ROS levels. This feature finds particular relevance in the therapeutic management of diabetic ulcers. Preliminary in vitro evaluation affirmed the hydrogel's biocompatibility and its potential to promote cell migration, inhibit apoptosis, and exhibit antibacterial properties. Further in vivo studies demonstrated that the PVA/SA/GO/GSH hydrogel could facilitate the healing of diabetic ulcer sites by mitigating oxidative stress and regulating glucose levels. Thus, the developed PVA/SA/GO/GSH hydrogel emerges as a promising candidate for diabetic ulcer treatment, owing to its specific bio-responsive traits and therapeutic efficacy.

Ethylene glycol derivative-pendanted quaternary ammonium antibacterial polymers with low cytotoxicity

Cationic poly(quaternary ammonium) (pQA) polymers exhibit excellent antibacterial efficacy but high cytotoxicity (thus low selectivity), hampering their widespread use as antibacterial agents. Herein, we systematically synthesized a series of pQA polymers (pQA−EG) containing biocompatible ethylene glycol (EG) derivative pendant groups with different chain lengths and connectivities (acyclic/cyclic). The antibacterial efficacy of pQA−EG was optimized by a moderate EG chain length, which endowed the polymer with balanced hydrophobicity/charge density. The high chain flexibility of the EG derivative combined with its good hydrophilicity was critical for significantly lowering the cytotoxicity of pQA−EG. Hence, compared with pQA polymers containing alkyl pendant groups, the pQA−EG polymer containing a long flexible EG derivative pendant group exhibited significantly lower cytotoxicity and higher selectivity as well as satisfactory antibacterial activity and kinetics. Our study offers a rational platform for synthesizing low-toxicity antibacterial polymers and provides fundamental insights into their structure−biological activity relationships.

Preparation of pH-sensitive nanogels bioconjugated with shark antibodies (VNAR) for targeted drug delivery with potential applications in colon cancer therapies.

Cancer is the second leading cause of death worldwide. To combat this disease, novel and specialized therapeutic systems are urgently needed. This is the first study to explore a system that combines shark variable domain (Fv) of new antigen receptor (VNAR) antibodies (hereinafter VNARs), PEGylated nanogels (pH-sensitive poly(N,N-diethylaminoethyl methacrylate, PDEAEM), and the anticancer drug 5-fluorouracil (5-FU) to explore its potential applications in colon cancer therapies. Nanogels were functionalized in a scalable reaction with an N-hydroxysuccinimide (NHS)-terminated polyethylene glycol derivative and bioconjugated with shark antibodies. Dynamic light scattering measurements indicated the presence of monodispersed nanogels (74 to 236 nm). All systems maintained the pH-sensitive capacity to increase in size as pH decreased. This has direct implications for the release kinetics of 5-FU, which was released faster at pH 5 than at pH 7.4. After bioconjugation, the ELISA results indicated VNAR presence and carcinoembryonic antigen (CEA) recognition. In vitro evaluations of HCT-116 colon cancer cells indicated that functionalized empty nanogels are not cytotoxic and when loaded with 5-FU, the cytotoxic effect of the drug is preserved. A 15% reduction in cell viability was observed after two hours of contact with bioconjugated nanogels when compared to what was observed with non-bioconjugated nanogels. The prepared nanogel system shows potential as an effective and site-specific nanocarrier with promising applications in in vivo studies of colon cancer therapies.

Engineered nanomicelles targeting proliferation and angiogenesis inhibit tumour progression by impairing the synthesis of ceramide-1-phosphate.

Tumour cells secrete various proangiogenic factors like VEGF, PDGF, and EGF that result in the formation of highly vascularized tumours with an immunosuppressive tumour microenvironment. As tumour growth and metastasis are highly dependent on angiogenesis, targeting tumour vasculature along with rapidly dividing tumour cells is a potential approach for cancer treatment. Here, we specifically engineered sub-100 sized nanomicelles (DTX-CA4 NMs) targeting proliferation and angiogenesis using an esterase-sensitive phosphocholine-tethered docetaxel conjugate of lithocholic acid (LCA) (PC-LCA-DTX) and a poly(ethylene glycol) (PEG) derivative of an LCA-combretastatin A4 conjugate (PEG-LCA-CA4). DTX-CA4 NMs effectively inhibit the tumour growth in syngeneic (CT26) and xenograft (HCT116) colorectal cancer models, inhibit tumour recurrence, and enhance the percentage survival in comparison with individual drug-loaded NMs. DTX-CA4 NMs enhance the T cell-mediated anti-tumour immune response and DTX-CA4 NMs in combination with an immune checkpoint inhibitor, anti-PDL1 antibody, enhance the anti-tumour response. We additionally showed that DTX-CA4 NMs effectively attenuate the production of ceramide-1-phosphate, a key metabolite of the sphingolipid pathway, by downregulating the expression of ceramide kinase at both transcriptional and translational levels. Therefore, this study presents the engineering of effective DTX-CA4 NMs for targeting the tumour microenvironment that can be explored further for clinical applications.

Deep Eutectic Solvents Consisting of a Dicationic Ionic Salt with Multiple Active Sites and Ethylene Glycol Derivatives for Reversible SO2 Absorption

Deep Eutectic Solvents Consisting of a Dicationic Ionic Salt with Multiple Active Sites and Ethylene Glycol Derivatives for Reversible SO₂ Absorption

Cutaneous anaphylactoid reaction to polyoxyethylene hydrogenated castor oil in dogs.

Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs. To determine the potential for HCO-ethoxylate-containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO-25, -40, -60 and -80). Four healthy male laboratory dogs. We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre-treatment with an antihistamine. All HCO-ethoxylate-containing drugs caused a wheal-and-flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO-ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO-60-induced reaction was suppressed by an oral antihistamine. The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision-making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect.

In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives

African trypanosomiasis is a significant vector-borne disease of humans and animals in the tsetse fly belt of Africa, particularly affecting production animals such as cattle, and thus, hindering food security. Trypanosoma congolense (T. congolense), the causative agent of nagana, is livestock's most virulent trypanosome species. There is currently no vaccine against trypanosomiasis; its treatment relies solely on chemotherapy. However, pathogenic resistance has been established against trypanocidal agents in clinical use. This underscores the need to develop new therapeutics to curb trypanosomiasis. Many nitroheterocyclic drugs or compounds, including nitrofurantoin, possess antiparasitic activities in addition to their clinical use as antibiotics. The current study evaluated the in vitro trypanocidal potency and in vivo treatment efficacy of previously synthesized antileishmanial active oligomeric ethylene glycol derivatives of nitrofurantoin. The trypanocidal potency of analogues 2a-o varied among the trypanosome species; however, T. congolense strain IL3000 was more susceptible to these drug candidates than the other human and animal trypanosomes. The arylated analogues 2k (IC50 0.04 µM; SI >6365) and 2l (IC50 0.06 µM; SI 4133) featuring 4-chlorophenoxy and 4-nitrophenoxy moieties, respectively, were revealed as the most promising antitrypanosomal agents of all analogues against T. congolense strain IL3000 trypomastigotes with nanomolar activities. In a preliminary in vivo study involving T. congolense strain IL3000 infected BALB/c mice, the oral administration of 100 mg/kg/day of 2k caused prolonged survival up to 18 days post-infection relative to the infected but untreated control mice which survived 9 days post-infection. However, no cure was achieved due to its poor solubility in the in vivo testing medium, assumably leading to low oral bioavailability. These results confirm the importance of the physicochemical properties lipophilicity and water solubility in attaining not only in vitro trypanocidal potency but also in vivo treatment efficacy. Future work will focus on the chemical optimization of 2k through the investigation of analogues containing solubilizing groups at certain positions on the core structure to improve solubility in the in vivo testing medium which, in the current investigation, is the biggest stumbling block in successfully treating either animal or human Trypanosoma infections.

Ligand-enabled palladium-catalysed enantioselective synthesis of α-quaternary amino and glycolic acids derivatives

Ligand-enabled palladium-catalysed enantioselective synthesis of α-quaternary amino and glycolic acids derivatives

Novel family of [RuCp(N,N)(P)]+ compounds with simultaneous anticancer and antibacterial activity: Biological evaluation and solution chemistry studies

A family of ten novel ruthenium(II)-cyclopentadienyl organometallics of general formula [Ru(η5-C5H5)(N,N)(PPh2(C6H4COOR)][CF3SO3] (1–10) in which (N,N) = 4,4′-R′-2,2′-bipyridyl (R = –H or –CH2CH2OH; R’ = –H, –CH3, –OCH3, –CH2OH, and –CH2-biotin) was prepared from [Ru(η5-C5H5)(PPh2(C6H4COOH))2Cl]. All compounds were fully characterized by means of several spectroscopic and analytical techniques, and the molecular structures of [Ru(η5-C5H5)(PPh2(C6H4COOH))2Cl], 1, 3 and 4 have been additionally studied by single-crystal X-ray diffraction. The anticancer activity of all compounds was evaluated in sensitive and multidrug-resistant counterpart cell lines from human colorectal cancer (Colo 205 and Colo 320) and non-small cell lung cancer NSCLC (A549, NCI–H460 versus NCI–H460/R) as well. Notably, compounds 6 and 7 (R CH2CH2OH and (N,N) = bipy or Me2bipy, respectively) showed antiproliferative effect against both cell lines with high intrinsic selectivity towards cancer cells. The antibacterial activity of all compounds was also evaluated against both Gram negative and Gram positive strains, and some compounds in the series showed potent antibacterial activity against Staphylococcus aureus strains, including the methicillin-resistant MRSA strains.Solution speciation studies revealed that the complexes bearing the PPh2(C6H4COO−) ligand are neutral at physiological pH (7.4) in contrast with their ethylene glycol derivatives that have a permanent positive charge. While all compounds are lipophilic, the difference in the distribution coefficient for neutral and charged complexes is around one order of magnitude. Complexes 6 and 7 exhibited excellent biological activity and were selected for further studies. Spectrofluorometric methods were used to investigate their interaction with biomolecules such as human serum albumin (HSA) and calf thymus DNA (ct-DNA). For these complexes, binding site II of HSA is a possible binding pocket through non-covalent interactions. The release of ethidium from the DNA adduct by the charged complexes proves their interaction with DNA in contrast to the neutral ones.In conclusion, Ru(II)-cyclopentadienyl complexes with 2,2′-bipyridyl-derivatives and an ethylene glycol moiety tethered to the phenylphosphane co-ligand are very promising from a therapeutic perspective, in particular complexes 6 and 7 that display remarkable antibacterial activity with a high anti-proliferative effect against colon and non-small cell lung cancers, both clinically challenging neoplasias in need of effective solutions.

Soft-hard complex microsphere strategy to construct high-temperature form-stable phase change material for melt-spun temperature-regulating fibers

Phase change materials (PCMs) have excellent temperature regulation ability and are usually used in smart wearable devices. However, PCMs prepared by traditional methods cannot be applied to high-temperature (>230 °C) melt spinning, and leakage of PCM is prone to occur during spinning. This work successfully prepared a series of PCMs with high thermal form-stable by the strategy of capillary adsorption of inorganic porous materials and surface microchemical crosslinking and proved that it can effectively solve the above-mentioned problems of high-temperature melt-spinning temperature regulating fibers. This PCM prepared by combining porous SiO2 adsorption and chemical crosslinking of polyethylene glycol derivatives exhibits excellent heat resistance at 130 °C for 40 min. In addition, polycaprolactam (PA6) was selected as the polymer matrix, and PA6-based temperature regulating fibers with excellent temperature regulating functions were prepared. The thermal response time of the fabric prepared from this fiber in the hot environment is 782 s, and the maximum temperature difference is 5.4 °C. Moreover, the exothermic duration in cold environment is 427 s, and the maximum temperature difference is 2.3 °C. This shows that the prepared temperature regulating fiber has good application prospect in heat-regulating devices.

Nanosized Assemblies from Amphiphilic Solanesol Derivatives for Anticancer Drug Delivery.

Unexpected functionalities of pharmaceutical excipients have been found in some cases. Preplanned introduction of excipients with therapeutic effects might not only reduce the risks of metabolism-related toxicity but also provide synergistic therapeutic effects. Herein, natural original solanesol (SOL), one of the isoprene compounds with some pharmacological activities, was selected to prepare a series of amphiphilic derivatives by chemical modification, and drug delivery systems for oncotherapy were established. Three derivatives, including solanesyl bromide (SOL-Br), monosolanesolsolanesyl succinate (MSS), and solanesylthiosalicylate (STS), were synthesized and formulated into nanosized self-assemblies for doxorubicin (DOX) encapsulation. Meanwhile, polyethylene glycol (PEG) derivatives were synthesized as the stabilizer of solanesol-based self-assemblies, among which hydrazine-poly(ethylene glycol)-hydrazine (PEG6000-DiHZ) was found to be more reliable. The optimized molar ratio between PEG6000-DiHZ and solanesol derivatives was found to be 2:1, considering the drug-loading capacity of self-assemblies. Consistent release profiles were found for the DOX-loaded self-assemblies, in which about 75-80% DOX was cumulatively released within 60 h at pH 5.0. The three DOX-loaded self-assemblies were found to be homogeneous spheres with average particle sizes in the range of 100-200 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Blank self-assemblies were found to have an inhibiting ability toward MCF-7 and HepG-2 cancer cells, which might originate from the inherent nature of solanesol derivatives. In vivo pharmacodynamic experiments demonstrated that blank self-assemblies had certain inhibitory effect on tumor growth compared with the controls. Further enhanced effects were also found for the drug-loaded self-assemblies due to the synergistic anti-tumor effect existing between the drug and the carriers. This work has presented a simple and effective strategy to prepare a therapeutic carrier by direct assembling of the therapeutic compound without PEGylation steps, by which the therapeutic carrier materials could take their effect directly and synergistically along with the loaded drugs.

Cancer immunotheranostics using bioactive nanocoated photosynthetic bacterial complexes

Developing new modalities that allow multidimensional therapy with optical and immunological regulations is a challenge ahead of pharmacology and drug discovery for effective cancer treatment. To this end, superior purple photosynthetic bacteria, which show unique near-infrared (NIR) fluorescence, strong photothermal conversion ability, and high biocompatibility, were screened from various bacterial strains. To improve the therapeutic performances of screened bacteria, we further designed and developed simple chemical bacterial membrane functionalization with bioactive molecules and polyethylene glycol derivatives. Exploring the physicochemical and physiological properties of the chemically functionalized bacteria complexes achieved excellent tumor targeting and strong anticancer efficacies. The highly biocompatible functional bacteria showed cytotoxic immunological effects, strong NIR fluorescence, and powerful photothermal conversion in the targeted tumor milieu under biologically penetrating NIR light irradiation.

Synergistic effect and enhanced safety of double dynamic solid polymer electrolytes for lithium metal batteries

A solid polymer electrolyte with low mechanical strength and poor flexibility will cause mechanical degradation, short circuits, or functional failures in lithium ion batteries (LIBs). Therefore, introducing an double dynamic solid polymer electrolytes with high ionic conductivity, good mechanical strength, and excellent self-healing ability for stabilizing the solid electrolyte interface, preventing battery fire, and suppressing Li dendrite growth will further improve the reliability, security, and lifetime of the LIBs. Herein, a series of dual dynamic self-healing solid polymer electrolytes (DD-shSPEs) are developed via the Schiff base reaction between different molar ratios of polyethylene glycol derivative (tat-PEG) and terephthalaldehyde. The hydrogen bond and the highly reversible imine bonds endow DD-shSPEs with rapid self-repairing capacity to cure mechanical damage within 5 min at normal temperature. The self-healing polymer electrolytes also exhibit excellent stretchability, which can satisfy the external deformation of the battery. Meanwhile, after self-healing, the ionic conductivities of the electrolytes can hold the original values. Also, the initial discharge capacity (IDC) of the battery based on DD-shSPEs reach to 149.3 mAh g-1 under a current rate of 0.1 C, and still maintains 144.2 mAh g−1 after 100 cycles. Besides, the polymer electrolyte (PE) also exhibits good interfacial stability and have a cycle life of more than 650 h at a current density of 0.2 mA cm-2. Accordingly, this work shows that the high-performance PE based on self-healing materials is promising for constructing high stable solid-state energy storage device.

Discrete polyethylene glycol derivatives as a potent impetus for next-generation biomedicines

PEGylation, which covalently modifies small-molecule drugs, peptides and proteins with polyethylene glycol (PEG) to improve their pharmacokinetics and efficacy, has become one of the most widely used drug modification techniques. However, PEG and its derivatives have been verified to be immunogenic and antigenic, which directly lead to side effects such as accelerated blood clearance (ABC) phenomenon and allergic reactions to PEGylated drugs or PEG excipients. Recent development of single molecular weight discrete PEG synthesis methodology have led to continuous and extensive focus on the difference in biological activity between conventional polydisperse PEG and single molecular weight precise PEG. Discrete PEG has demonstrated obvious advantages in resisting protein adsorption, cell adhesion and enhancing drug efficacy. These preliminary results not only confirm the significant impact of PEG chain polydispersity on its biological effect, but also reveal the possibility and potential advantages of using discrete PEG to reduce the immunogenicity and antigenicity. Hopefully, single chemical structure and molecular weight ensure the batch repeatability of newly developed discrete PEG products, and facilitate the understanding of their physicochemical properties and biological effects that promoting the clinical conversion of precise PEG drugs.