A single-chain fab derived drug conjugate for HER2 specific delivery.

Despite the development of antibody-drug conjugates, the fragment Fab-based drug conjugates offer some unique capabilities in terms of safety, clearance, penetration and others. Current methods for preparing Fab drug conjugates are limited by the availability and stability of Fab proteins, leaving reports on this rare. Here, we found that a single-chain scaffold of Fab enables stabilization of the paired structure and supports high-yield expression in bacteria cytoplasm. Furthermore, we conjugated anti-neoplastic agent SN38 to the C-terminus by sortase A ligation and generated a homogenous Fab conjugate with the drug-to-Fab ratio of 1. The resulting anti-HER2 Fab-SN38 conjugate demonstrated potent and antigen-dependent cell-killing ability with the aid of its special cathepsin-triggered cyclization-promoted release mechanism. In vivo, Fab-SN38 can prevent growths of HER2-positive tumors in athymic mice and be well tolerated to the treatment at 7 mg/kg per dose. Anti-tumor activity, high dose tolerance and penetration advantage observed in this study would merit Fab conjugate investigation in target chemotherapy.

Oligonucleotide-Linked Lipid Nanoparticles as a Versatile mRNA Nanovaccine Platform.

An effective delivery platform is crucial for the development of mRNA vaccines and therapeutics. Here, a versatile platform utilizing cholesterol-modified oligonucleotides (L-oligo) that bind to the mRNA within lipid nanoparticles (LNP), and enables the effective delivery of the mRNA into target cells is introduced. mRNA incorporated into LNPs via linkage with L-oligo, termed oligonucleotide-linked LNP (lnLNP), is superior in cellular uptake and transfection efficiency in target cells in vitro and in vivo, compared to the conventional LNP formulations. It is further applied lnLNP as an mRNA vaccine platform for SARS-CoV-2, demonstrating robust induction of neutralizing activity as well as polyfunctional SARS-CoV-2-specific T-cell response in vivo. The current strategy can be versatilely applied to different LNP platforms, for vaccine and therapeutic applications against various diseases, such as infections and cancers.

Structure, Surface Topography, and Glass Transition Temperature of Dental Poly (Methyl Methacrylate) Resin Conjugated with 3,9-bisethenyl-2,4,8,10-tetraoxaspiro [5,5] Undecane as Cross-linker: An In Vitro Research.

AIM AND OBJECTIVES: To characterize and analyze the structural presentation of a new denture base copolymer with a spiro-acetal cross-linker at 10 and 20 wt.% concentrations by nuclear magnetic resonance (NMR) and field emission scanning electron microscopy-energy-dispersive X-ray (FESEM-EDX) spectroscopies. Also, to evaluate the glass transition temperature (TG) of the new copolymer. MATERIALS AND METHODS: The investigational groups G10 and G20 were heat-cured with the new spiro-acetal cross-linker at the above-mentioned concentrations, respectively. The control group G0 was heat-cured without the new cross-linker. Nuclear magnetic resonance and EDX spectroscopies determined the copolymerization along with elemental composition. The surface characteristics were discerned by FESEM. Differential scanning calorimetry was employed to evaluate the TG of the resultant copolymer. Appropriate statistical operations were performed to compare the mean TG of the groups. RESULTS: The new copolymer's structure with the spiro-acetal cross-linker was configured with protons, carbons, aluminum, zirconium, yttrium, and silicon atoms. The TG of the resultant copolymer was high when compared with the G0. The 20 wt.% spiro-acetal cross-linker in the copolymer exhibited the highest TG. CONCLUSION: The spiro-acetal cross-linking comonomer incorporated in the heat-cure denture polymer produced a new denture base copolymer with elevated TG. The resultant configuration of the new copolymer was characterized, structurally presented, and confirmed. CLINICAL SIGNIFICANCE: The new copolymer might exhibit augmented strength due to the copolymerized spiro-acetal cross-linker. Moreover, the smooth and regular surface of the copolymer would have minimum or negligible microbial adhesion due to the hydrophobicity of the spiro-acetal comonomer incorporated in the denture base composition. How to cite this article: Ravivarman C, Ajay R, Saatwika L, et al. Structure, Surface Topography, and Glass Transition Temperature of Dental Poly (Methyl Methacrylate) Resin Conjugated with 3,9-bisethenyl-2,4,8,10-tetraoxaspiro [5,5] Undecane as Cross-linker: An In Vitro Research. J Contemp Dent Pract 2024;25(5):486-493.

Preclinical evaluation of a new technetium-99m labeled neurotensin analogue for NTSR1 targeted radionuclide imaging.

Neurotensin is a regulatory peptide that can act as a growth factor on different types of normal and cancerous cells. Binding of Neurotensin to relevant receptors leads to cell proliferation, survival, migration and invasion by changing intracellular enzyme activity. Therefore, the design of a neurotensin-based radiopeptide plays an important role in targeted imaging or therapy of neurotensin receptor-positive tumors. A [Lys8]-neurotensin (7-13) peptide was synthesized and attached to HYNIC as a chelator via a linker. The labeling procedure was carried out at 100 °C for 10 min using 99mTc as a radionuclide and EDDA/tricine as coligands. Stability of the labeled peptide in human serum was determined using RTLC and HPLC methods. The receptor binding internalization was studied using HT-29 colon carcinoma cells, and tissue biodistribution was evaluated in mice bearing CT-26 tumors. The [99mTc]Tc-Tricine/EDDA/HYNIC-GABA-[Lys8]-neurotensin (7-13) peptide demonstrated a labeling yield of over 98 %, a specific activity of 37.00 GBq/µmol, high stability in human serum, a nanomolar range of Kd, and a tumor uptake of 0.36 ± 0.15 % ID/g at 1-h post-injection. These results suggest that the labeled peptide is a suitable imaging agent for neurotensin receptor-positive tumors.

Defect-Engineered MOF-801/Sodium Alginate Aerogel Beads for Boosting Adsorption of Pb(II).

Metal-organic frameworks (MOFs) are attractive adsorbents for heavy metal capture due to their superior stability, easy modification, and adjustable pore size. However, their inherent microporous structure poses challenges in achieving a higher adsorption capacity. Defect engineering is considered a simple method to create hierarchical MOFs with larger pores. Here, we employed l-aspartic acid as a mixed linker to bind Zr4+ clusters in competition with fumaric acid of MOF-801 to create defects, and the pore size was increased from 4.66 to 15.65 nm. Mercaptosuccinic acid was subsequently used as a postexchange ligand to graft the resultant MOF-801 by acid-ammonia condensation to further expand the pore size to 22.73 nm. Notably, the -NH2, -COOH, and -SH groups contributed by these two ligands increased the adsorption sites for Pb(II). The obtained defective MOF-801 with larger pores was thereafter loaded onto sodium alginate to form aerogel beads as adsorbents, and an adsorption capacity of 375.48 mg/g for Pb(II) was achieved, which is ∼51 times that of pristine MOF-801. The aerogel beads also exhibited outstanding reusability with a removal efficiency of ∼90.23% after 5 cycles of use. The adsorption mechanism of Pb(II) included ion-exchange interaction, as well as chelation interactions of Pb-O, Pb-NH2, and Pb-S. The versatile combination of defect engineering and composite beads provides novel inspirations for MOF modification for boosting heavy metal adsorption.

Cryopreservation of bovine sperm causes single-strand DNA breaks that are localized in the toroidal regions of chromatin.

BACKGROUND: Sperm cryopreservation is widely used in the cattle industry, as it allows for disassociating the localization of sires and the collection of semen from the timing of artificial insemination. While freeze-thawing is known to impair sperm DNA integrity, whether the damage induced consists of single- (SSB) or double-strand breaks (DSB) has not been determined. In addition, no previous study has addressed if DNA breaks preferentially reside in specific genome regions such as those forming the toroid linker regions, or are rather spread throughout the regions linked to protamines. The main aim of the present work, therefore, was to elucidate the type and localization of the DNA damage generated by cryopreservation and to evaluate its impact on artificial insemination outcomes in cattle. RESULTS: The incidence of SSB and DSB was evaluated in 12 ejaculates before and after cryopreservation with the Comet assay, and the localization of the DNA breaks was assessed using pulsed-field gel electrophoresis (PFGE). Before cryopreservation, the incidence of SSB was 10.99% ± 4.62% and involved 20.56% ± 3.04% of sperm cells, whereas these figures significantly (P < 0.0001) increased up to 34.11% ± 3.48% and 53.36% ± 11.00% in frozen-thawed sperm. In contrast, no significant differences in the incidence of DSB were observed (P > 0.990) before and after cryopreservation (before: incidence of 13.91% ± 1.75% of sperm DNA affecting 56.04% ± 12.49% of sperm cells; after: incidence of 13.55% ± 1.55% of sperm DNA involving 53.36% ± 11.00% of sperm cells). Moreover, PFGE revealed that the percentage of sperm DNA fragments whose length was shorter than a toroid (< 31.5 kb) was greater (P < 0.0001) after (27.00% ± 4.26%) than before freeze-thawing (15.57% ± 4.53%). These differences indicated that the DNA breaks induced by cryopreservation affect the regions condensed in protamines, which are structured in toroids. On the other hand, in vivo fertility rates were associated to the incidence of SSB and DSB in frozen-thawed sperm (P = 0.032 and P = 0.005), but not with the size of the DNA fragments resulting from these breaks (P > 0.05). CONCLUSION: Cryopreservation of bovine sperm generates single-strand DNA breaks, which are mainly located in protamine-condensed toroidal regions. The incidence of DNA breaks in cryopreserved sperm has an impact on cattle fertility, regardless of the size of generated fragments.

Unraveling the nexus of nesprin in dilated cardiomyopathy: From molecular insights to therapeutic prospects.

Dilated cardiomyopathy is a complex and debilitating heart disorder characterized by the enlargement and weakening of the cardiac chambers, leading to impaired contractility and heart failure. Nesprins, a family of nuclear envelope spectrin repeat proteins that include isoforms Nesprin-1/-2, are integral components of the LInker of Nucleoskeleton and Cytoskeleton complex. They facilitate the connection between the nuclear envelope and the cytoskeleton, crucial for maintaining nuclear architecture, migration and positioning, and mechanical transduction and signaling. Nesprin-1/-2 are abundantly expressed in cardiac and skeletal muscles.They have emerged as key players in the pathogenesis of dilated cardiomyopathy. Mutations in synaptic nuclear envelope-1/-2 genes encoding Nesprin-1/-2 are associated with dilated cardiomyopathy, underscoring their significance in cardiac health. This review highlights the all known cases of Nesprin-1/-2 related dilated cardiomyopathy, focusing on their interactions with the nuclear envelope, their role in mechanical transduction, and their influence on gene expression. Moreover, it delves into the underlying mechanisms through which Nesprin dysfunction disrupts nuclear-cytoskeletal coupling, leading to abnormal nuclear morphology, impaired mechanotransduction, and altered gene regulation. The exploration of Nesprin's impact on dilated cardiomyopathy offers a promising avenue for therapeutic interventions aimed at ameliorating the disease. This review provides a comprehensive overview of recent advancements in understanding the pivotal role of Nesprins in dilated cardiomyopathy research.

Covalent labeling of Matrix Metalloproteases with affinity-based probes containing tuned reactive N-acyl-N-alkyl sulfonamide cleavable linkers.

Original covalent probes with an N-acyl-N-alkyl sulfonamide cleavable linker were developed to target a broad set of human Matrix Metalloproteases (MMPs). The electrophilicity of this cleavable linker was modulated to improve the selectivity of the probes as well as reduce their unspecific reactivity in complex biological matrices. We first demonstrated that targeting the S3 subsite of MMPs enables access to broad-spectrum affinity-based probes that exclusively react with the active version of these proteases. The probes were further assessed in proteomes of varying complexity, where human MMP-13 was artificially introduced at known concentration and the resulting labeled MMP was imaged by in-gel fluorescence imaging. We showed that the less reactive probe was still able to covalently modify MMP-13 while exhibiting reduced off-target unspecific reactivity. This study clearly demonstrated the importance of finely controlling the reactivity of the NASA warhead to improve the selectivity of covalent probes in complex biological systems.

Docetaxel-tethered di-Carboxylic Acid Derivatised Fullerenes: A Promising Drug Delivery Approach for Breast Cancer.

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63 nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use.

Antimetastatic and antitumor activities of oncolytic NDV AMHA1 in a 3D culture model of breast cancer.

Introduction: Newcastle disease virus (NDV) AMHA1 is capable of killing cancer cells by direct replication or induction of apoptosis alongside other pathways. In this study, we report the potent antimetastatic and anticancer activities of NDV AMHA1 in a 3D spheroid model of breast cancer metastasis. Methods: we used two breast cancer cell lines AMJ13 and MCF7 in our metastasis model system. Results: First, we showed that NDV AMHA1 can infect and kill breast cancer cells in proliferating adherent cells and tumor spheroids using different virus doses and studying virus replication kinetics. We showed that NDV can infect and spread within the spheroids that represent metastasis before and after reattachment. Furthermore, we evaluated the ability of NDV to induce apoptosis in cancer spheroids and by virus tracking showed that NDV infection is essential for the elimination of these metastasis spheroids. Discussion: The mechanism by which NDV induces cell killing in the metastasis model is the induction of caspase-3 and P21 and inhibition of Ki67 in cancer cells, but not in normal cells. In conclusion, these results indicate that NDV AMHA1 has the ability to kill breast cancer metastases in suspension or attached, and this is a novel finding of NDV AMHA1 being a possibly efficient therapy against human metastatic breast cancer.

A tailored cytochrome P450 monooxygenase from Gordonia rubripertincta CWB2 for selective aliphatic monooxygenation.

Cytochrome P450 monooxygenases are recognized as versatile biocatalysts due to their broad reaction capabilities. One important reaction is the hydroxylation of non-activated C-H bonds. The subfamily CYP153A is known for terminal hydroxylation reactions, giving access to functionalized aliphatics. Whilst fatty derivatives may be converted by numerous enzyme classes, midchain aliphatics are seldomly accepted, a prime property of CYP153As. We report here on a new CYP153A member from the genome of the mesophilic actinobacterium Gordonia rubripertincta CWB2 as an efficient biocatalyst. The gene was overexpressed in Escherichia coli and fused with a surrogate electron transport system from Acinetobacter sp. OC4. This chimeric self-sufficient whole-cell system could perform hydroxylation and epoxidation reactions: conversions of C6-C14 alkanes, alkenes, alcohols and of cyclic compounds were observed, yielding production rates of, e.g., 2.69 mM h-1 for 1-hexanol and 4.97 mM h-1 for 1,2-epoxyhexane. Optimizing the linker compositions between the protein units led to significantly altered activity. Balancing linker length and flexibility with glycine-rich and helix-forming linker units increased 1-hexanol production activity to 350 % compared to the initial linker setup with entirely helical linkers. The study shows that strategic coupling of efficient electron supply and a selective enzyme enables previously challenging monooxygenation reactions of midchain aliphatics.

An Enhanced Retroviral Vector for Efficient Genetic Manipulation and Selection in Mammalian Cells.

Introducing genetic material into hard-to-transfect mammalian cell lines and primary cells is often best achieved through retroviral infection. An ideal retroviral vector should offer a compact, selectable, and screenable marker while maximizing transgene delivery capacity. However, a previously published retroviral vector featuring an EGFP/Puromycin fusion protein failed to meet these criteria in our experiments. We encountered issues such as low infection efficiency, weak EGFP fluorescence, and selection against infected cells. To address these shortcomings, we developed a novel retroviral vector based on the Moloney murine leukemia virus. This vector includes a compact bifunctional EGFP and Puromycin resistance cassette connected by a 2A peptide. Our extensively tested vector demonstrated superior EGFP expression, efficient Puromycin selection, and no growth penalty in infected cells compared with the earlier design. These benefits were consistent across multiple mammalian cell types, underscoring the versatility of our vector. In summary, our enhanced retroviral vector offers a robust solution for efficient infection, reliable detection, and effective selection in mammalian cells. Its improved performance and compact design make it an ideal choice for a wide range of applications involving precise genetic manipulation and characterization in cell-based studies.

Probing Defects in Covalent Organic Frameworks.

Defects in covalent organic frameworks (COFs) play a pivotal role in determining their properties and performance, significantly influencing interactions with adsorbates, guest molecules, and substrates as well as affecting charge carrier dynamics and light absorption characteristics. The present review focuses on the diverse array of techniques employed for characterizing and quantifying defects in COFs, addressing a critical need in the field of materials science. As will be discussed in this review, there are basically two types of defects referring either to missing organic moieties leaving free binding groups in the material or structural imperfections resulting in lower crystallinity, grain boundary defects, and incomplete stacking. The review summarizes an in-depth analysis of state-of-the-art characterization techniques, elucidating their specific strengths and limitations for each defect type. Key techniques examined in this review include powder X-ray diffraction (PXRD), infrared spectroscopy (IR), thermogravimetric analysis (TGA), nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), scanning transmission electron microscopy (STEM), scanning tunneling microscope (STM), high resolution transmission electron microcoe (HRTEM), gas adsorption, acid-base titration, advanced electron microscopy methods, and computational calculations. We critically assess the capability of each technique to provide qualitative and quantitative information about COF defects, offering insights into their complementary nature and potential for synergistic use. The last section summarizes the main concepts of the review and provides perspectives for future development to overcome the existing challenges.

A methamphetamine vaccine using short monoamine and diamine peptide linkers and poly-mannose.

Methamphetamine (METH) substance use disorder is a long-standing and ever-growing public health concern. Efforts to develop successful immunotherapies are ongoing with vaccines that generate strong antibody responses are an area of significant research interest. Herein, we describe the development of a METH Hapten conjugate vaccine comprised of either two short-length peptides as linkers and mannan as an immunogenic delivery carrier. Initially, Hapten 1 (with a monoamine linker) and Hapten 2 (with a diamine linker) were synthesised. Each step of the Hapten synthesis were characterized by LC-MS and purified by Flash Chromatography and the identity of the purified Haptens were confirmed by 1H NMR. Haptens were conjugated with mannan (a polymannose), and conjugation efficiency was confirmed by LC-MS, TLC, 1H NMR, and 2,4 DNPH tests. The immunogenic potential of the two conjugated vaccines were assessed in mice with a 3-dose regimen. Concentrations of anti-METH antibodies were measured by enzyme-linked immunosorbent assay. All the analytical techniques confirmed the identity of Hapten 1 and 2 during the synthetic phase. Similarly, all the analytical approaches confirmed the conjugation between the Haptens and mannan. Mouse immunogenicity studies confirmed that both vaccine candidates were immunogenic and the vaccine with the monoamine linker plus adjuvants induced the highest antibody response after the second booster.

A Universal Zwitterionic Cross-Linking Strategy for Designing Conductive Soft Electronics with Enhanced Mechanical Properties.

Ionogels are emerging as promising electronics due to their exceptional ionic conductivity, stretchability, and high thermal stability. However, developing ionogels with enhanced mechanical properties without compromising conductivity and ion transport rates remains a significant challenge. Here, we report a zwitterionic cross-linker, 4-(2-(((2-(methacryloyloxy)ethyl)carbamoyl)oxy)ethyl)-4,14-dimethyl-8,13-dioxo-7,12-dioxa-4,9-diazapentadec-14-en-4-ium-1-propanesulfonate (MEPS) and utilized it to cross-link a variety of functional monomers, leading to the synthesis of conductive ionogels that exhibit both high mechanical strength and versatile applicability. Due to its abundant hydrogen bond donors/acceptors and zwitterionic moiety, MEPS exhibits several hundred times higher solubility in ionic liquids compared to conventional cross-linkers. As a proof-of-concept, the poly(acrylic acid-MEPS) ionogels demonstrate enhanced elongation, fracture toughness, and superior thermal stability, all while maintaining high conductivity due to the high affinity between ionic liquids and zwitterionic networks. Furthermore, MEPS-cross-linked poly(α-thioctic acid) electronics can be engineered as strain sensors, showing exceptional antifatigue properties and recyclability, remaining stable and functional over 300 consecutive cycles. This universal cross-linking strategy not only improves the overall performance of ionogels but also contributes to the development of next-generation soft electronics with enhanced functionality and durability.

Tethering Cobalt Ions to BiVO4 Surface via Robust Organic Bifunctional Linker for Efficient Photoelectrochemical Water Splitting.

In the quest for efficient and stable oxygen evolution catalysts (OECs) for photoelectrochemical water splitting, the surface modification of BiVO4 is a crucial step. In this study, a novel and robust OEC, based on 3-(bis(pyridin-2-ylmethyl) amino) propanoic acid bifunctional linker known as dipicolyl alanine acid (DPAA) and cobalt ions, is prepared and fully characterized. The DPAA is anchored to the surface of BiVO4 and utilized to tether cobalt ions. The Co-DPAA/BiVO4 photoanode exhibits remarkable stability and efficiency toward photoelectrochemical water oxidation. Specifically, it showed anodic photocurrent increase of 7.1, 5.0, 3.0, and 1.3-fold at 1.23 VRHE as compared to pristine BiVO4, DPAA/BiVO4, Co-BiVO4, and Co-Pi/BiVO4 photoanodes, respectively. The photoelectrochemical and IMPS studies revealed that the Co-DPAA/BiVO4 photoanode exhibits a longer transient decay time for surface-trapped holes, higher charge transfer kinetics, and charge separation efficiency compared to Co-Pi/BiVO4 and pristine BiVO4 photoelectrodes. This indicates that the Co-DPAA effectively reduces surface recombination and facilitates charge transfer. Moreover, at 1.23 VRHE, the Co-DPAA/BiVO4 photoanode achieved a faradic efficiency of 92% for oxygen evolution reaction and could retain a turnover frequency of 3.65 s-1. The- exhibited effeciency is  higher than most of the efficient molecular oxygen evolution catalyst based on Ru.

Determination of degradation for sulfo-SIAB, SM(PEG)2, and sulfo-GMBS by RPLC-UV analysis.

Bi-functional N-Hydroxysuccinimide (NHS) linkers are widely used in the conjugation processes linking an immunogen with a carrier protein capable of boosting immunity. A potential vaccine candidate against HIV-1, called fusion peptide (FP), is covalently linked to the recombinant tetanus toxoid heavy-chain fragment C (rTTHC) via this type of linker. A reversed-phase liquid chromatography (RPLC-UV) method was used to monitor the linker's degradation kinetics in various buffers, mimicking the steps in the conjugation process. The kinetics of the reactivities of the linkers are revealed in this study and can provide a good guidance to help effective conjugation process before these linkers are completely hydrolyze to the inactive degradants. Three cross-linkers degradation pathways were evaluated: Sulfosuccinimidyl (4-iodoacetyl) aminobenzoate (Sulfo-SIAB), PEGylated SMCC (SM(PEG)2), and N-γ-maleimidobutyryl-oxysulfosuccinimide ester (Sulfo-GMBS). We have reported kinetics for Sulfo-SIAB.

Electrochemical Aptasensor with Antifouling Properties for Label-Free Detection of Oxytetracycline.

Oxytetracycline (OTC) is a widely employed antibiotic in veterinary treatment and in the prevention of infections, potentially leaving residues in animal-derived food products, such as milk, that are consumed by humans. Given the detrimental effects of prolonged human exposure to antibiotics, it has become imperative to develop precise and sensitive methods for monitoring the presence of OTC in food. Herein, we describe the development and results of a preliminary label-free electrochemical aptasensor with antifouling properties designed to detect OTC in milk samples. The sensor was realized by modifying a gold screen-printed electrode with α-lipoic acid-NHS and an amine-terminated aptamer. Different electrochemical techniques were used to study the steps of the fabrication process and to quantify OTC in the presence of the Fe(CN)64-/Fe(CN)63- redox couple The detectable range of concentrations satisfy the maximum residue limits set by the European Union, with an limit of detection (LOD) of 14 ng/mL in phosphate buffer (BP) and 10 ng/mL in the milk matrix, and a dynamic range of up to 500 ng/mL This study is a steppingstone towards the implementation of a sensitive monitoring method for OTC in dairy products.

Sensitive Coatings Based on Molecular-Imprinted Polymers for Triazine Pesticides' Detection.

Triazine pesticide (atrazine and its derivatives) detection sensors have been developed to thoroughly check for the presence of these chemicals and ultimately prevent their exposure to humans. Sensitive coatings were designed by utilizing molecular imprinting technology, which aims to create artificial receptors for the detection of chlorotriazine pesticides with gravimetric transducers. Initially, imprinted polymers were developed, using acrylate and methacrylate monomers containing hydrophilic and hydrophobic side chains, specifically for atrazine, which shares a basic heterocyclic triazine structure with its structural analogs. By adjusting the ratio of the acid to the cross-linker and introducing acrylate ester as a copolymer, optimal non-covalent interactions were achieved with the hydrophobic core of triazine molecules and their amino groups. A maximum sensor response of 546 Hz (frequency shift/layer height equal to 87.36) was observed for a sensitive coating composed of 46% methacrylic acid and 54% ethylene glycol dimethacrylate, with a demonstrated layer height of 250 nm (6.25 kHz). The molecularly imprinted copolymer demonstrated fully reversible sensor responses, not only for atrazine but also for its metabolites, like des-ethyl atrazine, and structural analogs, such as propazine and terbuthylazine. The efficiency of modified molecularly imprinted polymers for targeted analytes was tested by combining them with a universally applicable quartz crystal microbalance transducer. The stable selectivity pattern of the developed sensor provides an excellent basis for a pattern recognition procedure.

Nanomedicines with Versatile GSH-Responsive Linkers for Cancer Theranostics.

Glutathione (GSH)-responsive nanomedicines have generated significant interest in biochemistry, oncology, and material sciences due to their diverse applications, including chemical and biological sensors, diagnostics, and drug delivery systems. The effectiveness of these smart GSH-responsive nanomedicines depends critically on the choice of GSH-responsive linkers. Despite their crucial role, comprehensive reviews of GSH-responsive linkers are scarce, revealing a gap in the current literature. This review addresses this gap by systematically summarizing various GSH-responsive linkers and exploring their potential applications in cancer treatment. We provide an overview of the mechanisms of action of these linkers and their bioapplications, evaluating their advantages and limitations. The insights presented aim to guide the development of advanced GSH-responsive agents for cancer diagnosis and therapy.