Methoxy Poly Ethylene Glycol Research Articles

MXene Surface Engineering Enabling High‐Performance Solid‐State Lithium Metal Batteries

AbstractSolid polymer electrolytes (SPEs) offer inherent advantages for battery applications, such as high safety and excellent processability, but their practical use is limited by challenges like low ionic conductivity, subpar mechanical properties, and instability of the electrode/electrolyte interface. Here, novel SPEs are developed by embedding 2D MXenes decorated at the surface with methoxypolyethylene glycol chains into poly(vinylidene fluoride)‐hexafluoropropylene matrices, enhanced with succinonitrile as a plasticizer. This innovative design improves the compatibility of the modified MXene in poly(vinylidene fluoride)‐hexafluoropropylene and, together with the synergistic effects of succinonitrile, promotes the dissociation of lithium salt. The SPE achieves ionic conductivity of 1.49 × 10−4 S cm−1 at 30 °C, and a Li‐ion transference number of 0.59. These results are supported by comprehensive experimental characterization, COMSOL simulations, and DFT calculations. This SPE enables stable and reversible Li plating/stripping for over 2100 h in Li/Li symmetric cells, while fabricated Li/LiFePO4 full cells deliver a notable capacity of 135.4 mAh g−1 with an average Coulombic efficiency of 98.9% after 100 cycles at 0.2 C. Furthermore, the Li/LiNi0.6Co0.2Mn0.2O2 full cells also demonstrate a capacity of 140.5 mAh g−1 after over 200 cycles at 0.5 C, showcasing an impressive capacity retention rate of 99.6%.

An Adaptive Approach in Polymer-Drug Nanoparticle Engineering using Slanted Electrohydrodynamic Needles and Horizontal Spraying Planes.

The present study focuses on the adaptive development of a key peripheral component of conventional electrohydrodynamic atomisation (EHDA) systems, namely spraying needles (also referred to as nozzles or spinnerets). Needle geometry and planar alignment are often overlooked. To explore potential impact, curcumin-loaded polylactic-co-glycolic acid (PLGA) and methoxypolyethylene glycol amine (PEG)-based nanoparticles were fabricated. To elucidate these technological aspects, a horizontal electrospraying needle regime was adapted, and three formulations containing different polymeric ratios of PLGA: PEG (50:50, 75:25, and 25:75) were prepared and utilised. Furthermore, processing head tip geometries e.g.blunt (a flat needle exit) or slanted (a 45° inclination angle), were subjected to various flow rates (5 µL-100 µL). Successful engineering of curcumin-loaded polymeric nanoparticles (< 150nm) was observed. In-silico analysis demonstrated stable properties of curcumin, PEG and PLGA (molecular docking studies) and fluid flow direction towardsthe Taylor-Cone (also known as the stable jet mode), was shownby the assessment of fluid dynamics simulations in various needle outlets. Curcumin-loaded nanoparticles were characterised using an array of methods including Scanning electron microscopy, Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, as well as their contact angles, encapsulation efficiencies and finally release patterns. The discrepancy when spraying with blunt and angled needles was evidenced by electron micrographs and deposition patterns. Spraying plumes utilising slanted needles enhanced particle collection efficiency and distribution of resultant atomised structures. In addition to needle design, fine-tuning the applied voltage and flow rate impacted the electrospraying process. The coefficient of variation was calculated as 30.5% and 25.6% for blunt and angled needle outlets, respectively, presenting improved particle uniformity with the employment of angled needle tips (8-G needle at 25 µL). The interplay of processing parameters with the utilisation of a slanted exit at a capillary optimised the spray pattern and formation of desired nanoparticulates. These demonstrate great applicability for controlled deposition and up-scaling processes in the pharmaceutical industry. These advances elaborate on EHDA processes, indicating a more cost-effective and scalable approach for industrial applications, facilitating the generation of a diverse range of particle systems in a controlled and more uniform fashion.

Impact of Gold Nanoparticles Intraperitoneal Injection on Mice's Erythrocytes and Renal Tissue.

The purpose of this study was to investigate the effects of two different types of gold nanoparticles (AuNPs) delivered by intraperitoneal (IP) injection on blood and kidney tissue changes in a mouse model. Three groups of fifteen adult male BALB/c healthy mice, weighing approximately 25-30 g, were used for the experiment and designated G1, G2, and G3, respectively. G1 mice received vehicle, whereas G2 and G3 received an IP injection of 10 mg/kg body weight of methoxy poly ethylene glycol gold nanoparticles (PEG-AuNPs) and fluorescently dye labeled gold nanoparticles (Dye-AuNPs), respectively. Hematological parameters were measured based on the standard complete blood cell count (CBC) technique. The two nanoparticles, i.e., PEG-AuNPs and Dye-AuNPs, significantly reduced most red blood cell (RBC) parameters in the groups with the exception of a nonsignificant effect on hemoglobin (HBG) levels. Both gold nanoparticles, i.e., PEG-AuNPs and Dye-AuNPs, led to a reduced RBC count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) level when compared with the control. Notably, Dye-AuNPs and PEG-AuNPs resulted in a considerably higher RBC distribution RDW-(CV % and SD fL). Glomerular injury was suggested based on the development of hydropic degeneration and the presence of a protein-rich fluid inside the tubules. Renal tissue and blood indices changed significantly in response to the two nanoparticles, suggesting possible organ injury.

A Multifunctional Nanodrug Increases the Therapeutic Sensitivity of Lenvatinib to Hepatocellular Carcinoma by Inhibiting the Stemness of Hepatic Cancer Stem Cells.

Drug resistance resulting from diverse mechanisms including the presence of cancer stem cells (CSCs) is the main obstacle for improving therapeutic efficacy of lenvatinib in hepatocellular carcinoma (HCC). Herein, a nanomedicine (siCD24-Len-MnO@PLAP) is developed by incorporating manganese oxide (MnO), lenvatinib (Len), and siRNA against CD24 (siCD24) into micelles composed of methoxypolyethylene glycol (mPEG), poly-L-lysine (PLLys), and polyasparagyl(N-(2-Aminoethyl)piperidine) (PAsp(PIP)) triblock copolymer. The nanomedicine can respond to the tumor microenvironment (TME) to release lenvatinib, and produce Mn2+ and O2, accompanied by changes in nanoparticle charge, which facilitates cellular endocytosis of siCD24-loaded nanoparticles. The released siCD24 and lenvatinib synergistically reduces CD24 expression, resulting in a more pronounced inhibition of stemness of CSCs. In the mouse models of HCC using Huh7-derived CSCs and Hepa1-6-derived CSCs, the nanomedicine shows remarkable anti-cancer effect by enhancing the therapeutic effects of lenvatinib against HCC via reducing the expression level of CD24 and decreasing the expression of hypoxia inducible factor-1α (HIF-1α). Moreover, in situ production of paramagnetic Mn2+ from the nanomedicine serves as an excellent contrast agent for magnetic resonance imaging (MRI) to monitor the therapeutic process. This study demonstrates that this multifunctional MRI-visible siCD24- and lenvatinib-loaded nanodrug holds great potential in enhancing therapeutic sensitivity for HCC lenvatinib therapy.

Fe-HCOF-PEG2000 as a Hypoxia-Tolerant Photosensitizer to Trigger Ferroptosis and Enhance ROS-Based Cancer Therapy.

The hypoxic tumor microenvironment and single mechanisms severely limit the photodynamic therapy (PDT) efficiency of covalent organic framework (COF) nanoparticles in cancer treatment. Here, we propose an iron-loaded, hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000)-modified hollow covalent organic framework (HCOF), Fe-HCOF-PEG2000, for use in hypoxic PDT and ferroptosis therapy owing to its type I and II photodynamic ability and iron nanoparticle loading property. Fe-HCOF-PEG2000 nanoparticles (Fe-HCOFs-PEG2000) with semiconducting polymers and microporous skeletons allow efficient photophysical properties. Moreover, the iron nanoparticles on Fe-HCOF-PEG2000 caused ferroptosis and further enhanced tumor elimination under normoxic and hypoxic conditions. DSPE-PEG2000 endowed Fe-HCOF-PEG2000 with hydrophilicity, allowing it to circulate and accumulate in organs rich in blood supply, especially tumors. 808 nm NIR activated Fe-HCOF-PEG2000 aggregated in tumors and significantly inhibited tumor growth under hypoxia. To our knowledge, Fe-HCOF-PEG2000 is the leading combination of type I/II PDT and ferroptosis. The strong antitumor effects of this nanomaterial suggest prospects for clinical translation as a tumor nanotherapy drug.

페길화에 의한 재조합 산화환원 조절단백-1의 환원력 유지 최적화

PEGylation of recombinant proteins enhances their bioavailability by improving stability, solubility, and biological activity. This study aimed to optimize conditions for PEGylating apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) to preserve its reducing activity and ensure it remains non-immunogenic in vivo. The PEGylation reaction of recombinant APE1/Ref-1 showed a progressive pattern dependent on the molar ratio with methoxy polyethylene glycol (PEG)-succinimidyl-glutarate. Optimal PEGylation was achieved with a 30 molar ratio of PEG, modifying 29 lysine residues of recombinant APE1/Ref-1. Activity analysis demonstrated that PEGylated APE1/Ref-1 retained reducing activity for over 4 weeks under refrigerated conditions, comparable to its pre-preservation state. To evaluate the immunogenicity of PEGylated APE1/Ref-1 for in vivo applications, an enzyme linked immunosorbent assay confirmed that PEGylation did not alter its antigenicity. PEGylation is a critical strategy for developing biopharmaceuticals and is expected to be highly beneficial for in vivo applications.

Optimizing the Structure of a Pt Metal-Chelating Polymer to Reduce Nonspecific Binding for Mass Cytometry.

Mass cytometry is a bioanalytic tool based on atomic mass spectrometry for detecting biomarker expression on individual cells. Current reagents employ metal-chelating polymers binding isotopes of hard metal ions. Polymers bearing chelators for soft metal ions offer the promise for a large increase in multiplexing capabilities, but examples reported so far often have unacceptably high levels of nonspecific binding (NSB). We recently reported a new class of metal-chelating polymers with dipicolylamine (DPA) chelators that could bind Re and Pt. They also showed significant levels of NSB. Here, to reduce the NSB of the Pt-DPA polymer, we grafted water-soluble oligomers to the distal end of the dipicolylamine pendant group. Methoxy(polyethylene glycol) (DP = 24) was effective as was poly(sulfobetaine methacrylate) (DP = 29). Reacting the Pt-Cl bond of the metalated polymer with glutathione was remarkably effective at suppressing NSB. These results open the door to Pt-isotope-based metal-chelating polymers as new mass tags for mass cytometry.

Discovery of Biomarkers of a Recombinant Human Erythropoietin Administration to Thoroughbred Geldings by Label‐Free Proteomics

ABSTRACTErythropoiesis‐stimulating agents (ESAs) continue to be a significant threat to the integrity of human and equine sports. Besides conventional direct testing, monitoring the biomarkers associated with the effects of ESAs may provide a complementary approach via indirect detection to enhance doping control. In this study, we applied label‐free proteomics to discover plasma protein biomarkers in Thoroughbred geldings after administration with a long‐acting form of recombinant human erythropoietin (rhEPO), methoxy polyethylene glycol epoetin beta, Mircera. Increased haematocrit, haemoglobin and red blood cell (RBC) levels were evidenced as early as 4 days post‐administration in all three horses to varying extents. Tryptic peptides were obtained from plasma samples and analysed by nanoflow ultra‐high‐performance liquid chromatography–high‐resolution tandem mass spectrometry (nano‐UHPLC‐HRMSMS) using data‐independent acquisition. Differential protein abundance analysis has shortlisted seven protein biomarker candidates that showed significant changes specifically after Mircera administration in the treated but not in the control geldings, which comprised downregulation of two proteins, haptoglobin (HP) and haemopexin (HPX), and upregulation of five proteins, transferrin receptor 1 (TFR1), phospholipid transfer protein (PLTP), tenascin C (TNC), vascular cell adhesion molecule 1 (VCAM1) and galectin 3 binding protein (LGALS3BP). Multivariate analysis of plasma proteome has allowed the classification of control and treated samples. This is the first report on the discovery of plasma protein biomarkers of rhEPO administration to geldings. The results lay a foundation for applications of protein biomarkers for controlling the misuse of ESAs.

Fluorinated triphenylamine phthalocyanine @ silica-coated gold nanorods: A photoactivated lysosome escape and targeting mitochondria two-photon probe for imaging-guided photothermal synergistic photodynamic therapy in cancer cells

The timely evasion of nanomedicines from lysosomes is essential to avert premature degradation under the acidic and hydrolytic conditions characteristic of these cellular compartments. However, the development of effective strategies has been hindered by the complexity of design material and the scarcity of practical methods. In this study, we have synthesized a novel nanoparticle, designated as TPA-BPAF-SiPc@AuNR@SiO2. This nanoparticle was prepared by encapsulating near-infrared fluorinated triphenylamine-substituted silicon phthalocyanines (TPA-BPAF-SiPc) within mesoporous silica-coated gold nanorods (AuNR@SiO2). TPA-BPAF-SiPc@AuNR@SiO2 functions as a dual-function two-photon probe, facilitating photoactivated lysosome escape and targeting mitochondria. The inherent aggregation-induced emission (AIE) two-photon fluorescence of TPA-BPAF-SiPc is notably bright when encapsulated in AuNR@SiO2 nanocarriers, a phenomenon not observed in polymer nanocarriers composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) or in THF/water mixtures. Upon irradiation, this nanoparticle autonomously escapes from lysosomes and selectively targets mitochondria, a process can be visually monitored in real-time through the two-photon AIE fluorescence of TPA-BPAF-SiPc. Moreover, upon activation, TPA-BPAF-SiPc@AuNR@SiO2 produces a substantial quantity of reactive oxygen species (ROS) and induces hyperthermia effects, showcasing its potential for effective photodynamic therapy (PDT) in conjunction with synergistic hyperthermia. Flow cytometry data corroborate the induction of tumor cell death through both necrosis and apoptosis pathways by TPA-BPAF-SiPc@AuNR@SiO2. This study underscores the potential of TPA-BPAF-SiPc@AuNR@SiO2 as a multifunctional probe capable of enabling lysosome escape, mitochondria targeting, and two-photon fluorescence imaging-guided photothermal synergistic photodynamic therapy, specifically tailored for the treatment of breast cancer.

Multi-Walled Carbon Nanotubes Accelerate Leukaemia Development in a Mouse Model.

Inflammation is associated with an increased risk of developing various cancers in both animals and humans, primarily solid tumors but also myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Multi-walled carbon nanotubes (MWCNTs), a type of carbon nanotubes (CNTs) increasingly used in medical research and other fields, are leading to a rising human exposure. Our study demonstrated that exposing mice to MWCNTs accelerated the progression of spontaneous MOL4070LTR virus-induced leukemia. Additionally, similar exposures elevated pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and induced reactive oxygen species (ROS) in a murine macrophage cell line. These effects were significantly reduced in immunodeficient mice and when mice were treated with methoxypolyethylene glycol amine (PEG)-modified MWCNTs. These findings underscore the necessity of evaluating the safety of MWCNTs, particularly for those with hematologic cancers.

Enzyme-Responsive Micelles with High Drug-Loading Capacity for Antitumor Therapy.

To overcome the poor targeting of conventional chemotherapeutic drugs and the defects of low drug-loading capacity of conventional drug delivery systems, novel drug delivery systems with high drug-loading capacity are developed. Herein, the high drug-loaded mPEG79-GFLGDDD-DOX copolymer is first synthesized via an amide reaction, which can bond multiplex DOX. After PEGylation, the drug can resist the adsorption of proteins in the plasma in blood circulation, avoid being rapidly cleared out of the body, and prolong the circulation time of the drug in the blood, which is conducive to the enrichment of micelles in tumor tissues through the EPR effect. In tumor tissues, the peptide Glycine- Phenylalanine- Leucine- Glycine (GFLG) is recognized and sheared by overexpressed cathepsin B, which stripped the outer layer of methoxy polyethylene glycol (mPEG) and made it more readily available for uptake by tumor cells. After entering the tumor cells, the bonded DOX and the physically encapsulated DOX in the micelles played a synergistic role, realizing the killing of tumor cells, thus effectively enhancing the therapeutic effect on tumors. The findings in this work suggest that a high drug-loading drug delivery system has great potential in the clinical treatment of tumors.

Organic conjugated polymer nanoparticles enhanced tyrosinase electrochemical biosensor for selective, sensitive and rapid detection of bisphenol A

Bisphenol A (BPA) has been widely used in the production of polycarbonate (PC) plastics, flame retardants and epoxy resins, which is one of the most important endocrine disrupting chemicals and can cause damage to the estrogen system of human. In this work, organic conjugated polymer nanoparticles (CPNPs) were synthesized through nanoprecipitation method using liposome 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-mPEG2000) coated poly[(4,4′-bis(2-ethylhexyl)-dithieno[3,2-b:2′,3′-d]silole)-2,6-diyl-alt-4,7-di(4-hexyl-2-thienyl)-5,6-difluoro-2,1,3-benzothiadiazole] (PDTS-hDTBT) and poly[(4,4′-bis(2-ethylhexyl)-dithieno[3,2-b:2′,3′-d]silole)-2,6-diyl-alt-4,7-di(4-(2-ethylhexyl)-2-thienyl)-5,6-difluoro-2,1,3-benzothiadiazole] (PDTS-ehDTBT). These two polymers have different side chains, which can affect the configuration of the polymers, thereby affecting the π-π interaction between BPA and CPNPs. The resultant two CPNPs were explored as extremely attractive matrix for tyrosinase immobilization to construct electrochemical biosensing platforms for sensitive and rapid detection of BPA in water environments. The electrochemical performance of these two biosensors was significantly enhanced, benefiting from the large specific surface area and excellent biocompatibility of CPNPs, as well as the strong π-π interaction between CPNPs and BPA. The current response of PDTS-ehDTBT-Tyr-Chi/GCE exhibited a good linear relationship with BPA concentration ranging from 0.02 to 3.0 μM with a low detection limit of 11.83 nM and a high sensitivity of 0.9724 μA μM−1 cm−2. The fabricated biosensor was further used for BPA detection in actual samples with a recovery rate of 92.0 %–99.4 %. With the remarkable advantages, CPNPs-based biosensor provides a highly sensitive detection tool for rapid detection of BPA in actual samples, which has broad application prospects.

The angiogenic role of the alpha 9-nicotinic acetylcholine receptor in triple-negative breast cancers.

Nicotine acts as an angiogenic factor by stimulating endogenous cholinergic pathways. Several subtypes of nicotinic acetylcholine receptors (nAChRs) have been demonstrated to be closely correlated to the formation and progression of different types of cancers. Recently, several studies have found that nicotinic acetylcholine receptors α9 (α9-nAChRs) are highly expressed in breast tumors, especially in tumors derived from patients diagnosed at advanced stages. In vitro studies have demonstrated that activation of α9-nAChRs is associated with increased proliferation and migration of breast cancer. To study the tumor-promoting role of α9-nAChRs in breast cancers, we generated a novel anti-α9-nAChR and methoxy-polyethylene glycol (mPEG) bispecific antibody (α9 BsAb) for dissecting the molecular mechanism on α9-nAChR-mediated tumor progression. Unexpectedly, we discovered the angiogenic role of α9-nAChR in nicotine-induced neovascularization of tumors. It revealed α9 BsAbs reduced nicotine-induced endothelial cell tube formation, blood vessel development in Matrigel plug assay and angiogenesis in microtube array membrane murine model (MTAMs). To unbraid the molecular mechanism of α9-nAChR in nicotine-mediated angiogenesis, the α9 BsAbs were applied and revealed the inhibitory roles in nicotine-induced production of hypoxia-inducible factor-2 alpha (HIF-2α), vascular endothelial growth factor A (VEGF-A), phosphorylated vascular endothelial growth factor receptor 2 (p-VEGFR2), vascular endothelial growth factor receptor 2 (VEGFR2) and matrix metalloproteinase-9 (MMP9) from triple-negative breast cancer cells (MDA-MB-231), suggesting α9-nAChRs played an important role in nicotine-induced angiogenesis. To confirm our results, the shRNA targeting α9-nAChRs was designed and used to silence α9-nAChR expression and then evaluated the angiogenic role of α9-nAChRs. The results showed α9 shRNA also played an inhibitory effect in blocking the nicotine-induced angiogenic signaling. Taken together, α9-nAChR played a critical role in nicotine-induced angiogenesis and this bispecific antibody (α9 BsAb) may serve as a potential therapeutic candidate for treatments of the α9 positive cancers.

Fluorination Promotes Lithium Salt Dissolution in Borate Esters for Lithium Metal Batteries

Lithium metal batteries promise higher energy densities than current lithium-ion batteries but require novel electrolytes to extend their cycle life. To promote electrolyte stability against lithium metal and improve the reversibility of lithium deposition/stripping, several electrolyte design strategies have been pursued. For example, high concentration electrolytes (HCEs) and localized high concentration electrolytes (LHCEs) produce solvation structure rich in salt aggregates and ion pairs, which can increase lithium metal cycling Coulombic efficiency to as high as 99.5%. Recently, molecular design of fluorinated ether solvents also leads to high lithium metal Coulombic efficiency of up to 99.9% in single-solvent-single-salt ~ 1 M electrolytes. In addition, fluorinated acetals, fluorinated carbonates, and fluorinated sulfonamides are also reported to enable efficient lithium metal cycling. Among those novel electrolytes, fluorinated solvents or diluents are frequently used because fluorinated moieties are known to yield LiF as a preferable component in solid electrolyte interphase (SEI). However, fluorinated groups are believed to weaken ion solvation as most fluorinated solvents show poorer solvation ability or lower ionic conductivity compared to their nonfluorinated counterparts. The trade-off between SEI passivation and ion solvation limits further optimization of fluorinated electrolytes.In this work, we synthesize tris(2-fluoroethyl) borate (TFEB) as a new fluorinated borate ester solvent. Interestingly, moderately fluorinated TFEB shows unexpectedly high lithium salt solubility (~1 M LiFSA) while the nonfluorinated triethyl borate (TEB) and heavily fluorinated tris(2,2,2-trifluoroethyl) borate (TTFEB) can hardly dissolve lithium salt. Through density functional theory (DFT) calculations and ab-initio molecular dynamics (AIMD) simulations, we show that the partially fluorinated -CH2F group in TFEB acts as primary coordination site that promotes lithium salt dissolution. The electrochemical property of TFEB electrolyte is then compared to the methoxy polyethyleneglycol borate esters reported in literature. Owing to the fluorinated solvent structure, TFEB electrolyte passivates lithium metal with LiF-rich SEI and supports compact lithium deposition morphology, high lithium metal Coulombic efficiency, and stable cycling of lithium metal/LiFePO4 cells. This work ushers in a new electrolyte design paradigm where partially fluorinated moieties enable salt dissolution and can serve as primary ion coordination sites for next-generation electrolytes. Figure 1

Bioinspired nickel‐cysteine‐methoxy polyethylene glycol metallopolymer water solubility and electrochemical properties

AbstractThe exploitation of remarkable hydrogen evolution reaction (HER) catalysts that perform at rates comparable with that of platinum but utilize earth‐abundant metals in a green solvent (water) has garnered considerable interest. Inspired by enzymes, water‐soluble metallopolymers have recently emerged as highly promising HER catalysts, generally exhibiting high HER rates in aqueous solutions. However, challenges remain in the synthesis of metallopolymers and many artificial hydrogen evolution catalysts still rely on organic solvents. This study proposes incorporating water‐soluble methoxy polyethylene glycol at both ends of a nickel–cysteine metal complex through a classical esterification reaction. The resulting nickel metallopolymer demonstrates considerable water solubility (103.9 mg mL−1) under room temperature. Moreover, the stable metallopolymer exhibits an irreversible reduction peak between −0.6 and − 0.8 V, indicating HER activity in acidic and neutral environments. The excellent water solubility of this metallopolymer catalyst provides a basis for subsequent research and has practical applications in the field of HER catalysts.

ROS-responsive charge reversal mesoporous silica nanoparticles as promising drug delivery system for neovascular retinal diseases

Intravitreal injection of biodegradable implant drug carriers shows promise in reducing the injection frequency for neovascular retinal diseases. However, current intravitreal ocular devices have limitations in adjusting drug release rates for individual patients, thereby affecting treatment effectiveness. Accordingly, we developed mesoporous silica nanoparticles (MSNs) featuring a surface that reverse its charge in response to reactive oxygen species (ROS) for efficient delivery of humanin peptide (HN) to retinal epithelial cells (ARPE-19). The MSN core, designed with a pore size of 2.8 nm, ensures a high HN loading capacity 64.4% (w/w). We fine-tuned the external surface of the MSNs by incorporating 20% Acetyl-L-arginine (Ar) to create a partial positive charge, while 80% conjugated thioketal (TK) methoxy polyethylene glycol (mPEG) act as ROS gatekeeper. Ex vivo experiments using bovine eyes revealed the immobilization of Ar-MSNs-TK-PEG (mean zeta potential: 2 mV) in the negatively charged vitreous. However, oxidative stress reversed the surface charge to −25 mV by mPEG loss, facilitating the diffusion of the nanoparticles impeded with HN. In vitro studies showed that ARPE-19 cells effectively internalize HN-loaded Ar-MSNs-TK, subsequently releasing the peptide, which offered protection against oxidative stress-induced apoptosis, as evidenced by reduced TUNEL and caspase3 activation. The inhibition of retinal neovascularization was further validated in an in vivo oxygen-induced retinopathy (OIR) mouse model.

PEGylation renders carnosine resistant to hydrolysis by serum carnosinase and increases renal carnosine levels

Carnosine’s protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with diabetic kidney disease. In contrast to rodents however, carnosine is rapidly degraded by the carnosinase-1 enzyme. To overcome this hurdle, we sought to protect hydrolysis of carnosine by conjugation to Methoxypolyethylene glycol amine (mPEG-NH2). PEGylated carnosine (PEG-car) was used to study the hydrolysis of carnosine by human serum as well as to compare the pharmacokinetics of PEG-car and L-carnosine in mice after intravenous (IV) injection. While L-carnosine was rapidly hydrolyzed in human serum, PEG-car was highly resistant to hydrolysis. Addition of unconjugated PEG to carnosine or PEG-car did not influence hydrolysis of carnosine in serum. In mice PEG-car and L-carnosine exhibited similar pharmacokinetics in serum but differed in half-life time (t1/2) in kidney, with PEG-car showing a significantly higher t1/2 compared to L-carnosine. Hence, PEGylation of carnosine is an effective approach to prevent carnosine degradations and to achieve higher renal carnosine levels. However, further studies are warranted to test if the protective properties of carnosine are preserved after PEGylation.

Ratiometric electrochemical aptasensor with strand displacement for insulin detection in blood samples

BackgroundDiabetes patients suffer either from insulin deficiency or resistance with a high risk of severe long-term complications, thus the quantitative assessment of insulin level is highly desired for diabetes surveillance and management. Utilizing insulin-capturing aptamers may facilitate the development of affordable biosensors however, their rigid G-quadruplex structures impair conformational changes of the aptamers and diminish the sensor signals. ResultsHere we report on a ratiometric, electrochemical insulin aptasensor which is achieved by hybridization of an insulin-capturing aptamer and a partially complementary ssDNA to break the rigid G-quadruplex structures. To improve the durability of the aptasensor, the capturing aptamer was immobilized on gold electrodes via two dithiol-phosphoramidite functional groups while methoxy-polyethylene glycol thiol was used as a blocking molecule. The exposure of the sensor to insulin-containing solutions induced the dissociation of the hybridized DNA accompanied by a conformational rearrangement of the capturing aptamer back into a G-quadruplex structure. The reliability of sensor readout was improved by the adoption of an AND logic gate utilizing anthraquinone and methylene blue redox probes associated to the aptamer and complementary strand, respectively. Our aptasensor possessed an improved detection limit of 0.15 nM in comparison to aptasensors without strand displacement. SignificanceThe sensor was adapted for detection in real blood and is ready for future PoC diagnostics. The capability of monitoring the insulin level in an affordably manner can improve the treatment for an increasing number of patients in developed and developing nations. The utilization of low-cost and versatile aptamer receptors together with the engineering of ratiometric electrochemical signal recording has the potential to considerably advance the current insulin detection technology toward multi-analyte diabetes sensors.

Nanoparticles-encapsulated doxorubicin alleviates drug resistance of osteosarcoma via inducing ferroptosis

To determine the effects of polymeric nanoparticle for doxorubicin (Dox) delivery and treatment of drug-resistant Osteosarcoma (OS) cells. Methoxy-polyethylene glycol amino (mPEG-NH2) and platinum bio-mimetic polycaprolactone-cysteine (PtBMLC) were crosslinked to obtain glutathione (GSH)-responsive mPEG-NH2-PtBMLC polymer to encapsulate Dox (named as Nano-Dox). The particle size and zeta potential of the nanoparticles were measured, and internalization of Dox by OS cells was observed. After treatment with Nano-Dox, cell proliferation was determined by cell counting kit 8 (CCK-8) and colony formation assay. Cell migration and invasion were determined by Transwell assay. Cell cycle arrest was assessed by flow cytometry. The induction of ferroptosis was analyzed by abnormal accumulation of total iron, Fe2+. Nano-Dox exhibited a stronger localization in OS cells (p < 0.01). Nano-Dox induced more significant suppression of drug-resistant OS cell growth (p < 0.01), migration (p < 0.01), and invasion (p < 0.01), compared with the single Dox treatment group, along with decreased expression of N-cadherin, Snail, and Vimentin, suggesting impaired cancer migration and invasion. The treatment with Nano-Dox induced notable cell cycle arrest at G0/G1 phase (p < 0.01) and accumulation of iron, Fe2+, and MDA (p < 0.01), as well as suppressed the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11. Administration of ferroptosis inhibitor (Fer-1) reversed the anti-proliferation effects of Nano-Dox (p < 0.01). The Dox delivered by the polymeric nanoparticle system notably enhanced its effects on suppressing the growth, migration, and invasion of drug-resistant OS cells via inducing ferroptosis. The application of environment response polymer enhanced the delivery of Dox and the therapeutic effects on OS.

Utilizing the allyl-terminated copolymer methoxy(poly(ethylene glycol))-block-poly(jasmine lactone) in the development of amorphous solid dispersions: A comparative study of functionalized and non-functionalized polymer

Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong molecular interactions with drugs. Polymers tailored to fit the physicochemical properties of the drug molecule to be incorporated, for instance by allowing the incorporation of specific functional groups, would be highly sought-for in this regard. For this purpose, the novel allyl-terminated polymer methoxy(polyethylene glycol)-block-poly(jasmine lactone) (mPEG-b-PJL) has been synthesized and functionalized to potentially enhance specific drug-polymer interactions. This study investigated the use of mPEG-b-PJL in ASDs, using carvedilol (CAR), a weakly basic model drug. The findings revealed that the acidic functionalized form of the polymer (mPEG-b-PJL-COOH) indeed established stronger molecular interactions with CAR compared to its non-functionalized counterpart mPEG-b-PJL. Evaluations on polymer effectiveness in forming ASDs demonstrated that mPEG-b-PJL-COOH outperformed its non-functionalized counterpart in miscibility, drug loading ability, and stability, inferred from reduced molecular mobility. However, dissolution tests indicated that ASDs with mPEG-b-PJL-COOH did not significantly improve the dissolution behaviour compared to amorphous CAR alone, despite potential solubility enhancement through micelle formation. Overall, this study confirms the potential of functionalized polymers in ASD formulations, while the challenge of improving dissolution performance in these ASDs remains an area of further development.