N-hydroxysuccinimide Ester Research Articles

Investigation and comparison of graphene nanoribbon and carbon nanotube based SARS-CoV-2 detection sensors: An ab initio study

The rapid detection of SARS-CoV-2, the pathogen of the Covid-19 pandemic, is obviously of great importance for stopping the spread of the virus by detecting infected individuals. Here, we report the ab initio analysis results of graphene nanoribbon (GNR) and carbon nanotube (CNT) based SARS-CoV-2 detection sensors which are experimentally demonstrated in the literature. The investigated structures are the realistic molecular models of the sensors that are employing 1-pyrenebutyric acid N-hydroxysuccinimide ester as the antibody linker. Density functional theory in conjunction with non-equilibrium Green's function formalism (DFT-NEGF) is used to obtain the transmission spectra, current-voltage and resistance-voltage characteristics of the sensors before and after the attachment of the SARS-CoV-2 spike protein. The operation mechanism of the GNR and CNT based SARS-CoV-2 sensors are exposed using the transmission spectrum analysis. Moreover, it is observed that GNR based sensor has more definitive detection characteristics compared to its CNT based counterpart.

In Situ-Forming Collagen-Hyaluronate Semi-Interpenetrating Network Hydrogel Enhances Corneal Defect Repair.

PurposeMillions worldwide suffer vision impairment or blindness from corneal injury, and there remains an urgent need for a more effective and accessible way to treat corneal defects. We have designed and characterized an in situ-forming semi-interpenetrating polymer network (SIPN) hydrogel using biomaterials widely used in ophthalmology and medicine.MethodsThe SIPN was formed by cross-linking collagen type I with bifunctional polyethylene glycol using N-hydroxysuccinimide ester chemistry in the presence of linear hyaluronic acid (HA). Gelation time and the mechanical, optical, swelling, and degradation properties of the SIPN were assessed. Cytocompatibility with human corneal epithelial cells and corneal stromal stem cells (CSSCs) was determined in vitro, as was the spatial distribution of encapsulated CSSCs within the SIPN. In vivo wound healing was evaluated by multimodal imaging in an anterior lamellar keratectomy injury model in rabbits, followed by immunohistochemical analysis of treated and untreated tissues.ResultsThe collagen-hyaluronate SIPN formed in situ without an external energy source and demonstrated mechanical and optical properties similar to the cornea. It was biocompatible with human corneal cells, enhancing CSSC viability when compared with collagen gel controls and preventing encapsulated CSSC sedimentation. In vivo application of the SIPN significantly reduced stromal defect size compared with controls after 7 days and promoted multilayered epithelial regeneration.ConclusionsThis in situ-forming SIPN hydrogel may be a promising alternative to keratoplasty and represents a step toward expanding treatment options for patients suffering from corneal injury.Translational RelevanceWe detail the synthesis and initial characterization of an SIPN hydrogel as a potential alternative to lamellar keratoplasty and a tunable platform for further development in corneal tissue engineering and therapeutic cell delivery.

One-Step Conversion of NHS Esters to Reagents for Site-Directed Labeling of IgG Antibodies.

Antibody conjugates are extensively used for diagnostics and therapeutics, and as a tool for molecular biology. To prepare such conjugates N-hydroxysuccinimide (NHS) esters are most often used due to the straightforward experimental procedure and the commercial accessibility of the reagents. Such conjugates are however highly heterogeneous, since only the reactivity of the lysines determines the distribution of labels. This has inspired the development of methods that experimentally are as facile but produce conjugates of higher quality. Herein, we report the development of a reagent that can, in one step, be activated with an NHS ester of choice and subsequently can be directly used for site-directed labeling of antibodies. The reagent can be prepared in three synthetic steps and produces conjugates with similar ease as for NHS esters, however in a site-directed manner. We show that the reagent is quantitatively activated by a variety of NHS esters, and we use these to functionalize IgG1, IgG2, and IgG4 antibodies.

Colorimetric Detection of the SARS-CoV-2 Virus (COVID-19) in Artificial Saliva Using Polydiacetylene Paper Strips.

The spread and resurgence of the SARS-CoV-2 virus (COVID-19 disease) threatens human health and social relations. Prevention of COVID-19 disease partly relies on fabricating low-cost, point-of-care (POC) sensing technology that can rapidly and selectively detect the SARS-CoV-2 virus. We report a colorimetric, paper-based polydiacetylene (PDA) biosensor, designed to detect SARS-CoV-2 spike protein in artificial saliva. Analytical characterizations of the PDA sensor using NMR and FT-IR spectroscopy showed the correct structural elucidation of PCDA-NHS conjugation. The PDA sensor platform containing the N-Hydroxysuccinimide ester of 10, 12-pentacosadiynoic acid (PCDA-NHS) was divided into three experimental PCDA-NHS concentration groups of 10%, 20%, and 30% to optimize the performance of the sensor. The optimal PCDA-NHS molar concentration was determined to be 10%. The PDA sensor works by a color change from blue to red as its colorimetric output when the immobilized antibody binds to the SARS-CoV-2 spike protein in saliva samples. Our results showed that the PDA sensing platform was able to rapidly and qualitatively detect the SARS-CoV-2 spike protein within the concentration range of 1 to 100 ng/mL after four hours of incubation. Further investigation of pH and temperature showed minimal influence on the PDA sensor for the detection of COVID-19 disease. After exposure to the SARS-CoV-2 spike protein, smartphone images of the PDA sensor were used to assess the sensor output by using the red chromatic shift (RCS) of the signal response. These results indicate the potential and practical use of this PDA sensor design for the rapid, colorimetric detection of COVID-19 disease in developing countries with limited access to medical testing.

Development of Safirinium dyes for new applications: fluorescent staining of bacteria, human kidney cells, and the horny layer of the epidermis

Low-molecular synthetic fluorophores are convenient tools in bioimaging applications. Several derivatives of Safirinium dyes as well as their reactive N-hydroxysuccinimide (NHS) esters bearing diverse substituents were synthesized and evaluated experimentally in terms of their lipophilicity by means of reverse-phase and immobilized artificial membrane high-performance liquid chromatography. Subsequently, the selected compounds were employed as novel cellular imaging agents for staining Gram-positive and Gram-negative bacteria, human kidney cell line, as well as human skin tissue. The analyzed dyes allowed for visualization of cellular structures such as mitochondria, endoplasmic reticulum, and cellular nuclei. They proved to be useful in fluorescent staining of stratum corneum, especially in the aspect of xenobiotic exposure and its penetration into the skin. The best results were obtained with the use of moderately lipophilic NHS esters of Safirinium Q. The development of Safirinium dyes is a promising alternative for commercially available dyes since the reported molecules have low molecular masses and exhibit efficient staining and remarkable water solubility. Moreover, they are relatively simple and low-cost in synthesis.

PEG Conjugated Zein Nanoparticles for In Vivo Use.

Zein can be utilized to form nanoscale particles for drug delivery applications. Despite the ease of synthesis, these particles often aggregate when exposed to physiologically relevant conditions (e.g., pH and salt concentrations). This instability has prevented their further development in applications requiring intravenous administration. To mitigate this colloidal instability, this research explored Zein nanoparticles (NP)s that were modified with polyethylene glycol (PEG) either through functionalized PEG pre- or post-NP formation. The results suggest that the pre-functionalization of the Zein using N-hydroxysuccinimide ester terminated PEG is the method of choice for synthesizing Zein NPs with conjugated PEG (Zein:PEG-Zein NPs). Zein:PEG-Zein NPs formed using this method displayed excellent stability in physiologically relevant conditions over 72 h and were stable at 4 °C for at least 3 months. When the NPs were cultured with cells for 72 h, no cytotoxicity or early signs of apoptosis were identified. Cellular uptake of the Zein:PEG-Zein NPs did not seem to be impacted by the amount of PEG incorporated in the NP but were concentration-, time-, and temperature-dependent. The lowest percent, stable Zein:PEG-Zein NP formulation (80% unmodified Zein and 20% PEG-modified Zein) induced no observable toxicity over 14 days in CD-1 mice dosed at 70 mg/kg via the tail vein. However, repeat dose pharmacokinetic (PK) studies demonstrated that following the first dose, the second dose caused health issues that required euthanasia shortly after administration. For those animals that survived, there was faster plasma elimination of the Zein:PEG-Zein NPs. Despite this, the Zein:PEG-Zein NPs represent a significantly improved formulation approach, one that displays a long circulation half-life and is suitable for single-use administration. Repeat dose applications will require additional methods to silence the immune response that is generated when using these NPs intravenously.

Rational Design of Porous Poly(ethylene glycol) Films as a Matrix for ssDNA Immobilization and Hybridization.

Poly(ethylene glycol) (PEG) films, fabricated by thermally induced crosslinking of amine- and epoxy-terminated four-arm STAR-PEG precursors, were used as porous and bioinert matrix for single-stranded DNA (ssDNA) immobilization and hybridization. The immobilization relied on the reaction between the amine groups in the films and N-hydroxy succinimide (NHS) ester groups of the NHS-ester-decorated ssDNA. Whereas the amount of reactive amine groups in the films with the standard 1:1 composition of the precursors turned out to be too low for efficient immobilization, it could be increased noticeably using an excess (2:1) concentration of the amine-terminated precursor. The respective films retained the bioinertness of the 1:1 prototype and could be successfully decorated with probe ssDNA, resulting in porous, 3D PEG-ssDNA sensing assemblies. These assemblies exhibited high selectivity with respect to the target ssDNA strands, with a hybridization efficiency of 78–89% for the matching sequences and full inertness for non-complementary strands. The respective strategy can be applied to the fabrication of DNA microarrays and DNA sensors. As a suitable transduction technique, requiring no ssDNA labeling and showing high sensitivity in the PEG-ssDNA case, electrochemical impedance spectroscopy is suggested.

Palladium-Catalyzed Synthesis of Esters from Arenes through C-H Thianthrenation.

The efficient palladium-catalyzed synthesis of esters from readily available arenes has been developed. These C-H bond esterifications were achieved relying on the regioselective thianthrenation to generate the aryl-TT salts, which were treated as reactive electrophilic substrates to couple with phenol formate and N-hydroxysuccinimide (NHS) formate giving access to phenol esters and NHS esters, respectively, in the absence of carbon monoxide. A wide range of functional esters could be prepared with high efficiency under this redox-neutral palladium-catalytic condition. Late-stage functionalization and investigations of synthetic applications demonstrated the potential application of the established platform and these products.

Development of a Bacterial Enzyme‐Based Biosensor for the Detection and Quantification of Selenate

An enzymatic biosensor has been developed for the determination of selenate (SeO4 2- ), in which selenate reductase (SeR) is chemically attached to a gold disk electrode by lipoic acid N-hydroxysuccinimide ester as linker, allowing the catalytic reduction of the SeO4 2- to SeO3 2- . Modification of the gold electrode was characterized by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), and electrochemistry. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements were performed in different buffers for selenate determination. Under optimum conditions, the calibration curve was linear over the range 7.0-3900.0 μg L-1 with limits of detection and quantification of 4.97 and 15.56 μg L-1 , respectively. The possible interference of the relevant oxyanions SO4 2- , NO3 - , NO2 - , PO4 3- and AsO4 3- in the determination of SeO4 2- was studied. Finally, the proposed biosensor was used to determine SeO4 2- with recovery between 95.2 and 102.4 % in different real water samples.

Synthesis of smart carriers based on tryptophan-functionalized magnetic nanoparticles and its application in 5-fluorouracil delivery

Multifunctional nanocarriers, specifically for tumor targeting and traceable features, have been increasingly considered in cancer therapies. Herein, a novel targeting agent (TA), tryptophan (TRP), was proposed for the synthesis of functionalized (3-aminopropyl) triethoxysilane-iron oxide nanoparticles using two methods, creating a smart drug delivery system (DDS). In one method, two-step, glutaraldehyde (GA) as a linker, bonded TRP and amino-functionalized magnetite, and in the second method, one step, TRP binding was carried out by (3-dimethyl aminopropyl)-N’-ethyl carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester. The synthesis yield of the second method was 7% higher than the first method. After synthesizing DDS, 5-fluorouracil (5-FU) was loaded on nanocarriers and was observed TRP functionalized nanoparticles by GA have better loading efficiency, which was 50% greater than the product from the one-step method. A pH-sensitive release profile was also studied for 5-FU/DDS with the release of almost 75% and 50% at pH 5.5 and 7.4, respectively. To analyze the biological aspects of nanocarriers, human breast cancer, MCF-7, and embryonic kidney, HEK293, cell lines were used for cellular uptake and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. In vitro studies confirmed that TRP can act as a TA as its cellular uptake through cancerous cells was 40% greater than normal cells, and the MTT assay confirmed that using DDS can increase and decrease the cell viability of normal cells and cancerous cells, respectively, compared to free drug. Therefore, it was concluded that advanced nano-assembly is a great candidate for breast cancer cell-targeted delivery.

Ammonium enrichment and recovery from synthetic and real industrial wastewater by amine-modified thin film composite forward osmosis membranes

In this study, we aimed to recover and enrich NH4+ from real wastewater using forward osmosis (FO). Positively-charged thin film composite (TFC) membranes were developed via chemical grafting with positively-charged polyethyleneimine (PEI). The TFC membrane surface was first activated using 1-ethyl-3-(3-dimethylaminopropyl) carboimide (EDC) and n-hydroxysuccinimide (NHS) to convert the carboxyl groups of polyamide into amine-reactive NHS esters. PEI grafting significantly increased the NH4+ retention in the feed solution. To further improve the NH4+ rejection, quaternization of the amine functional groups of PEI was conducted with iodomethane. Quaternization was found to further increase NH4+ rejection, up to over 98.5%, while maintaining similar water permeability with the PEI-grafted TFC membrane. Fouling control of the pristine and amine-modified TFC membranes were also demonstrated, and the quaternary amine-modified TFC membrane exhibited superior fouling resistance against organic and biological foulants. The amine-modified TFC membranes were evaluated for applicability for dewatering and NH4+ enrichment of real industrial wastewater. NH4+ enrichment using the PEI-grafted membranes was observed following wastewater dewatering, indicating the high NH4+ retention ability of the TFC membranes modified via amine grafting and quaternization. Wastewater dewatering of 90.3 and 92.4% were achieved using TFC-PEI-10 and TFC-qPEI, respectively.

New free radical-initiated peptide sequencing (FRIPS) mass spectrometry reagent with high conjugation efficiency enabling single-step peptide sequencing

A newly designed TEMPO-FRIPS reagent, 4-(2,2,6,6-tetramethylpiperidine-1-oxyl) methyl benzyl succinic acid N-hydroxysuccinimide ester or p-TEMPO–Bn–Sc–NHS, was synthesized to achieve single-step free radical-initiated peptide sequencing mass spectrometry (FRIPS MS) for a number of model peptides, including phosphopeptides. The p-TEMPO–Bn–Sc–NHS reagent was conjugated to target peptides, and the resulting peptides were subjected to collisional activation. The peptide backbone dissociation behaviors of the MS/MS and MS3 experiments were monitored in positive ion mode. Fragment ions were observed even at the single-step thermal activation of the p-TEMPO–Bn–Sc–peptides, showing mainly a-/x- and c-/z-type fragments and neutral loss ions. This confirms that radical-driven peptide backbone dissociations occurred with the p-TEMPO–Bn–Sc–peptides. Compared to the previous version of the TEMPO reagent, i.e., o-TEMPO–Bz–C(O)–NHS, the newly designed p-TEMPO–Bn–Sc–NHS has better conjugation efficiency for the target peptides owing to its improved structural flexibility and solubility in the experimental reagents. An energetic interpretation using the survival fraction as a function of applied normalized collision energy (NCE) ascertained the difference in the thermal activation between p-TEMPO–Bn–Sc– and o-TEMPO–Bz–C(O)– radical initiators. This study clearly demonstrates that the application of the p-TEMPO–Bn–Sc– radical initiator can improve the duty cycle, and this FRIPS MS approach has the potential to be implemented in proteomics studies, including phosphoproteomics.

Context-Dependence of the Reactivity of Cysteine and Lysine Residues.

The S‐alkylation of Cys residues with a maleimide and the N ϵ‐acylation of Lys residues with an N‐hydroxysuccinimide (NHS) ester are common methods for bioconjugation. Using Cys and Lys derivatives as proxies, we assessed differences in reactivity depending on the position of Cys or Lys in a protein sequence. We find that Cys position is exploitable to improve site‐selectivity in maleimide‐based modifications. Reactivity decreases substantially in the order N‐terminal>in‐chain>C‐terminal Cys due to modulation of sulfhydryl pK a by the α‐ammonium and carboxylate groups at the termini. A lower pK a value yields a larger fraction thiolate, which promotes selectivity while somewhat decreasing thiolate nucleophilicity in accord with βnuc =0.41. Lowering pH and salt concentration enhances selectivity still further. In contrast, differences in the reactivity of Lys towards an NHS ester were modest due to an appreciable decrease in amino group nucleophilicity with a lower pK a of its conjugate acid. Hence, site‐selective Lys modification protocols will require electrophiles other than NHS esters.

In-situ formed elastin-based hydrogels enhance wound healing via promoting innate immune cells recruitment and angiogenesis.

Harnessing the inflammation and angiogenesis is extremely important in wound healing. In this study, we developed bioactive elastin-based hydrogels which can recruit and modulate the innate immune cells and accelerate angiogenesis in the wound site and subsequently improve wound regeneration. These hydrogels were formed by visible-light cross-linking of acryloyl-(polyethylene glycol)-N-hydroxysuccinimide ester modified elastin with methacrylated gelatin, in order to mimic dermal microenvironment. These hydrogels showed highly tunable mechanical properties, swelling ratios and enzymatic degradation profiles, with moduli within the range of human skin. To mimic the in vivo degradation of the elastin by elastase from neutrophils, in vitro co-culture of the hydrogels and neutrophils was conducted. The derived conditioned medium containing elastin derived peptides (EDP-conditioned medium) promoted the expression of both M1 and M2 markers in M1 macrophages in vitro. Additionally, the EDP-conditioned medium induced superior tube formation of endothelia cells in Matrigel. In mice wound model, these elastin-based hydrogels attracted abundant neutrophils and predominant M2 macrophages to the wound and supported their infiltration into the hydrogels. The outstanding immunomodulatory effect of the elastin-based hydrogels resulted in superior angiogenesis, collagen deposition and dermal regeneration. Hence, these elastin-based hydrogels can be a promising regenerative platform to accelerate wound repair.

Fluorescent Imaging of Extracellular Fungal Enzymes Bound onto Plant Cell Walls.

Lignocelluloytic enzymes are industrially applied as biocatalysts for the deconstruction of recalcitrant plant biomass. To study their biocatalytic and physiological function, the assessment of their binding behavior and spatial distribution on lignocellulosic material is a crucial prerequisite. In this study, selected hydrolases and oxidoreductases from the white rot fungus Phanerochaete chrysosporium were localized on model substrates as well as poplar wood by confocal laser scanning microscopy. Two different detection approaches were investigated: direct tagging of the enzymes and tagging specific antibodies generated against the enzymes. Site-directed mutagenesis was employed to introduce a single surface-exposed cysteine residue for the maleimide site-specific conjugation. Specific polyclonal antibodies were produced against the enzymes and were labeled using N-hydroxysuccinimide (NHS) ester as a cross-linker. Both methods allowed the visualization of cell wall-bound enzymes but showed slightly different fluorescent yields. Using native poplar thin sections, we identified the innermost secondary cell wall layer as the preferential attack point for cellulose-degrading enzymes. Alkali pretreatment resulted in a partial delignification and promoted substrate accessibility and enzyme binding. The methods presented in this study are suitable for the visualization of enzymes during catalytic biomass degradation and can be further exploited for interaction studies of lignocellulolytic enzymes in biorefineries.

A rapid and robust method for amino acid quantification using a simple N-hydroxysuccinimide ester derivatization and liquid chromatography-ion mobility-mass spectrometry.

The vast majority of mass spectrometry (MS)-based metabolomics studies employ reversed-phase liquid chromatography (RPLC) to separate analytes prior to MS detection. Highly polar metabolites, such as amino acids (AAs), are poorly retained by RPLC, making quantitation of these key species challenging across the broad concentration ranges typically observed in biological specimens, such as cell extracts. To improve the detection and quantitation of AAs in microglial cell extracts, the implementation of a 4-dimethylaminobenzoylamido acetic acid N-hydroxysuccinimide ester (DBAA-NHS) derivatization agent was explored for its ability to improve both analyte retention and detection limits in RPLC-MS. In addition to the introduction of the DBAA-NHS labeling reagent, a uniformly (U)13C-labeled yeast extract was also introduced during the sample preparation workflow as an internal standard (IS) to eliminate artifacts and to enable targeted quantitation of AAs, as well as untargeted amine submetabolome profiling. To improve method sensitivity and selectivity, multiplexed drift-tube ion mobility (IM) was integrated into the LC-MS workflow, facilitating the separation of isomeric metabolites, and improving the structural identification of unknown metabolites. Implementation of the U-13C-labeled yeast extract during the multiplexed LC-IM-MS analysis enabled the quantitation of 19 of the 20 common AAs, supporting a linear dynamic range spanning up to three orders of magnitude in concentration for microglial cell extracts, in addition to reducing the required cell count for reliable quantitation from 10 to 5 million cells per sample.

Detection of carbohydrate antigen 19-9 by a diamond solution-gate field-effect transistor sensor

Detection of carbohydrate antigen 19-9 (CA19-9) via hydrogen-terminated diamond (H-diamond) solution-gate field-effect transistor (SGFET) sensor had been carried out for the first time. Linker molecule 1-pyrenebutyric acid–N-hydroxy succinimide ester (Pyr-NHS) was fixed on the surface of H-diamond by π-π bonding. Then, anti-CA19-9 antibody was immobilized with Pyr-NHS. After specific binding of CA19-9 and antibody, transfer characteristics of H-diamond SGFET exhibited a gate voltage shift in negative direction at the same output current. The sensitivity of sensor was obtained as −50.98 mV/Log10[antigen concentration]. The minimum detection concentration was 0.001 U/mL. This article illustrated a potential application of H-diamond SGFET sensor in CA19-9 detection.

Characterization of protein unfolding by fast cross-linking mass spectrometry using di-ortho-phthalaldehyde cross-linkers

Chemical cross-linking of proteins coupled with mass spectrometry is widely used in protein structural analysis. In this study we develop a class of non-hydrolyzable amine-selective di-ortho-phthalaldehyde (DOPA) cross-linkers, one of which is called DOPA2. Cross-linking of proteins with DOPA2 is 60–120 times faster than that with the N-hydroxysuccinimide ester cross-linker DSS. Compared with DSS cross-links, DOPA2 cross-links show better agreement with the crystal structures of tested proteins. More importantly, DOPA2 has unique advantages when working at low pH, low temperature, or in the presence of denaturants. Using staphylococcal nuclease, bovine serum albumin, and bovine pancreatic ribonuclease A, we demonstrate that DOPA2 cross-linking provides abundant spatial information about the conformations of progressively denatured forms of these proteins. Furthermore, DOPA2 cross-linking allows time-course analysis of protein conformational changes during denaturant-induced unfolding.

Her3-specific affibody mediated tumor targeting delivery of ICG enhanced the photothermal therapy against Her3-positive tumors

Photothermal therapy (PTT), mediated by tumor-targeted drug delivery of indocyanine green (ICG), is a promising strategy for cancer therapy. Human epidermal growth factor receptor 3 (Her3) is highly expressed in several solid tumors and is an ideal target for tumor diagnosis and therapy. This study prepared a Her3-specific dimeric affibody (ZHer3) using an Escherichia coli expression system. The affibody could bind explicitly to Her3-positive MCF7 and LS174T cells, rather than to Her3-negative SKOV-3 cells in vitro. ICG was coupled with the ZHer3 affibody (ICG-ZHer3) through an N-hydroxysuccinimide (NHS) ester reactive group for tumor-targeted delivery. As expected, Her3-positive cells were selectively and efficiently killed by ICG-ZHer3-mediated PTT in vitro. In vivo, ICG-ZHer3 preferentially accumulated in Her3-positive LS174T tumor grafts because of the tumor-targeting ability of the ZHer3 affibody. As a result of the local generation of cytotoxic reactive oxygen species and hyperthermia, the growth rates of LS174T tumor grafts were significantly inhibited by ICG-ZHer3-mediated PTT, and ICG-ZHer3 showed good safety performance during short-term treatment. In conclusion, these results demonstrated that ICG-ZHer3 is a promising photosensitizer for PTT against Her3-positive tumors.

Rapidly Self-Deactivating and Injectable Succinyl Ester-Based Bioadhesives for Postoperative Antiadhesion.

Postoperative adhesion not only causes severe complications for patients but also increases their economic burden. Injectable bioadhesives with adhesiveness to tissues can cover irregular wounds and stay stable in situ, which is a promising barrier for antiadhesion. However, the potential tissue adhesion caused by bioadhesives' indiscriminate adhesiveness between normal and wounded tissue is still a problem. Herein, by using poly(ethylene glycol) succinimidyl succinate (PEG-SS) and gelatin, a succinyl ester-based bioadhesive (SEgel) was fabricated with self-deactivating properties for postoperative antiadhesion. Because N-hydroxysuccinimide esters (NHS-esters) were used as the adhesive group, the bioadhesives' side in contact with the tissue built covalent anchors quickly to maintain the stability, but the superficial layer facing outward withstood fast hydrolysis and then lost its adhesion within minutes, avoiding the indiscriminate adhesiveness. In addition, because of the specific degradation behavior of succinyl ester, the SEgel with proper in vivo retention was achieved without the worry of causing foreign body reactions and unexpected tissue adhesion. Both the cecum-sidewall adhesion and hepatic adhesion models showed that the SEgel markedly reduced the severity of tissue adhesion. These results, together with the ease of the preparation process and well-proven biocompatibility of raw materials, revealed that the SEgel might be a promising solution for postoperative antiadhesion.