Comparative Evaluation of UV-Vis Spectroscopy-Based Approaches for Hemoglobin Quantification: Method Selection and Practical Insights.

The growing demand for effective alternatives to red blood cells (RBCs) has spurred significant research into hemoglobin (Hb)-based oxygen carriers (HBOCs). Accurate characterization of HBOCs-including Hb content, encapsulation efficiency, and yield-is crucial for ensuring effective oxygen delivery, economic viability, and the prevention of adverse effects caused by free Hb. However, the choice of quantification methods for HBOCs is often driven more by tradition than by a thorough assessment of available options.

An intranasal cationic liposomal polysaccharide vaccine elicits humoral immune responses against Streptococcus pneumoniae.

Diseases caused by S. pneumoniae are the leading cause of child mortality. As antibiotic resistance of S.

An in situ depot for the sustained release of a TLR7/8 agonist in combination with a TGFβ inhibitor promotes anti-tumor immune responses.

Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic TME, and the poor systemic tolerability of immune activating drugs are, however, fundamental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming an intratumoral sustained drug release depot that provides high payloads of immune stimulatory drugs selectively within the TME.

Nitric oxide-triggering activity of gold-, platinum- and cerium oxide-nanozymes from S-nitrosothiols and diazeniumdiolates.

Cardiovascular diseases pose a significant global health challenge, contributing to high mortality rates and impacting overall well-being and quality of life. Nitric oxide (NO) plays a pivotal role as a vasodilator, regulating blood pressure and enhancing blood flow-crucial elements in preventing cardiovascular diseases, making it a prime therapeutic target. Herein, metal-based nanozymes (NZs) designed to induce NO release from both endogenous and exogenous NO-donors are investigated.

Chemical synthesis of natural and azido-modified UDP-rhamnose and -arabinofuranose for glycan array-based characterization of plant glycosyltransferases.

Chemical syntheses of UDP-rhamnose and UDP-arabinofuranose and respective azido-modified analogues are reported. The prepared substrates are useful for the glycan array-based analysis of glycosyltransferases, as exemplified with the plant cell wall-biosynthetic enzymes XAT3, RRT4 and RRT5.

A novel PEG-mediated approach to entrap hemoglobin (Hb) within ZIF-8 nanoparticles: Balancing crystalline structure, Hb content and functionality.

Hemoglobin (Hb)-based oxygen carriers are investigated as a potential alternative or supplement to regular blood transfusions, particularly in critical and life-threatening scenarios. These include situations like severe trauma in remote areas, battlefield conditions, instances where blood transfusion is not feasible due to compatibility concerns, or when patients decline transfusions based on religious beliefs. This study introduces a novel method utilizing poly(ethylene glycol) (PEG) to entrap Hb within ZIF-8 nanoparticles (i.

Investigation of imaging the somatostatin receptor by opening the blood-brain barrier with melittin - A feasibility study using positron emission tomography and [Cu]Cu-DOTATATE.

DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors are found naturally in the intestines, pancreas, lungs, and brain (mainly cortex). In vivo measurement of the somatostatin receptors in the cortex has been challenging because available tracers cannot cross the blood-brain barrier (BBB) due to their intrinsic polarity.

Development and Preclinical Evaluation of [At]PSAt-3-Ga: An Inhibitor for Targeted α-Therapy of Prostate Cancer.

The application of prostate-specific membrane antigen (PSMA)-targeted α-therapy is a promising alternative to β-particle-based treatments. At is among the potential α-emitters that are favorable for this concept. Herein, At-based PSMA radiopharmaceuticals were designed, developed, and evaluated.

Synthesis of bioactive hemoglobin-based oxygen carrier nanoparticles via metal-phenolic complexation.

The transfusion of donor red blood cells (RBCs) is seriously hampered by important drawbacks that include limited availability and portability, the requirement of being stored in refrigerated conditions, a short shelf life or the need for RBC group typing and crossmatching. Thus, hemoglobin (Hb)-based oxygen (O) carriers (HBOCs) which make use of the main component of RBCs and the responsible protein for O transport, hold a lot of promise in modern transfusion and emergency medicine. Despite the great progress achieved, it is still difficult to create HBOCs with a high Hb content to attain the high O demands of our body.

Structural and functional alterations of polydopamine-coated hemoglobin: New insights for the development of successful oxygen carriers.

One of the major factors that is currently hindering the development of hemoglobin (Hb)-based oxygen carriers (HBOCs) is the autoxidation of Hb into nonfunctional methemoglobin. Modification with polydopamine (PDA), which is a biocompatible free radical scavenger has shown the ability to protect Hb against oxidation. Due to its tremendous potential in the development of successful HBOCs, herein, we conduct a thorough evaluation of the effect of PDA on the stability, aggregation, structure and function of the underlying Hb.

Hemoglobin-stabilized gold nanoclusters displaying oxygen transport ability, self-antioxidation, auto-fluorescence properties and long-term storage potential.

The development of hemoglobin (Hb)-based oxygen carriers (HBOCs) holds a lot of potential to overcome important drawbacks of donor blood such as a short shelf life or the potential risk of infection. However, a crucial limitation of current HBOCs is the autoxidation of Hb into methemoglobin (metHb), which lacks oxygen-carrying capacity. Herein, we address this challenge by fabricating a Hb and gold nanoclusters (AuNCs) composite (Hb@AuNCs) which preserves the exceptional features of both systems.

Small-molecule modulators of tumor necrosis factor signaling.

Tumor necrosis factor (TNF) is a pleiotropic cytokine with a major role in immune system homeostasis and is involved in many inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA), psoriasis, Alzheimer's disease (AD), and multiple sclerosis (MS). Thus, TNF and its receptors, TNFR1 and TNFR2, are relevant pharmacological targets. Biologics have been developed to block TNF-dependent signaling cascades, but they display serious side effects, and their pharmacological effectiveness decreases over time because of their immunogenicity.

Metal-organic framework-based oxygen carriers with antioxidant activity resulting from the incorporation of gold nanozymes.

Blood transfusions are a life-saving procedure since they can preserve the body's oxygen levels in patients suffering from acute trauma, undergoing surgery, receiving chemotherapy or affected by severe blood disorders. Due to the central role of hemoglobin (Hb) in oxygen transport, so-called Hb-based oxygen carriers (HBOCs) are currently being developed for situations where donor blood is not available. In this context, an important challenge that needs to be addressed is the oxidation of Hb into methemoglobin (metHb), which is unable to bind and release oxygen.

Targeting undruggable carbohydrate recognition sites through focused fragment library design.

Carbohydrate-protein interactions are key for cell-cell and host-pathogen recognition and thus, emerged as viable therapeutic targets. However, their hydrophilic nature poses major limitations to the conventional development of drug-like inhibitors. To address this shortcoming, four fragment libraries were screened to identify metal-binding pharmacophores (MBPs) as novel scaffolds for inhibition of Ca-dependent carbohydrate-protein interactions.

Covalent core-radiolabeling of polymeric micelles with I/At for theranostic radiotherapy.

Astatine-211 (At) is one of the most promising α-emitters for targeted alpha therapy, especially of cancer metastases. However, the lack of a stable isotope, frequent deastatination, and limited radiochemical knowledge makes it challenging to apply. Here, we report a new strategy for radiolabeling the lipophilic core of polymeric micelles (PMs) with covalently bound At.

Bioorthogonal Click of Colloidal Gold Nanoparticles to Antibodies In vivo.

Combining nanotechnology and bioorthogonal chemistry for theranostic strategies offers the possibility to develop next generation nanomedicines. These materials are thought to increase therapeutic outcome and improve current cancer management. Due to their size, nanomedicines target tumors passively.

Hemoglobin-based oxygen carriers camouflaged with membranes extracted from red blood cells: Optimization and assessment of functionality.

Despite being an indispensable clinical procedure, the transfusion of donor blood has important limitations including a short shelf-life, limited availability and specific storage requirements. Therefore, a lot of effort has been devoted to developing hemoglobin (Hb)-based oxygen carriers (HBOCs) that are able to replace or complement standard blood transfusions, especially in extreme life-threatening situations. Herein, we employed a Hb-loaded poly(lactide-co-glycolide) core which was subsequently coated with nanozymes to protect the encapsulated Hb from oxidation by reactive oxygen species.

Estimating the two graph dextran-stearic acid-spermine polymers based on iron oxide nanoparticles as carrier for gene delivery.

Non-viral gene carriers have shown noticeable potential in gene delivery because of limited side effects, biocompatibility, simplicity, and the ability to take advantage of electrostatic interactions. However, the low transfection rate of non-viral vectors under physiological conditions is controversial. This study aimed to decrease the transfection time using a static magnetic field.

Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis.

We describe the study of a novel aptamer-based candidate for treatment of seropositive rheumatoid arthritis. The candidate is a nanoparticle-formulated cyclic citrullinated peptide aptamer, which targets autoantibodies and/or the immune reactions leading to antibody production. Due to its specificity, the peptide aptamer nanoparticles might not interfere with normal immune functions as seen with other disease-modifying antirheumatic drugs.

Identification and Optimization of Novel Small-Molecule Cas9 Inhibitors by Cell-Based High-Throughput Screening.

CRISPR/Cas9 has revolutionized several areas of life science; however, methods to control the Cas9 activity are needed for both scientific and therapeutic applications. Anti-CRISPR proteins are known to inhibit the CRISPR/Cas adaptive immunity; however, delivery of such proteins is problematic. Instead, small-molecule Cas9 inhibitors could serve as useful tools due to their permeable, proteolytically stable, and non-immunogenic nature.

A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B.

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11-17 steps, 1.5-2.

Quantifying the heterogeneity of enzymatic dePEGylation of liposomal nanocarrier systems.

Lipid nanoparticles have been clinically successful in particular recently within the vaccine field, but better tools are needed to analyze heterogeneities at the single particle level to progress drug delivery designs to the next level. Especially, liposomal nanocarriers are becoming increasingly complex e.g.

Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists.

Systemic administration of toll-like receptor (TLR) agonists have demonstrated impressive preclinical results as an anti-cancer therapy due to their potent innate immune-stimulatory properties. The clinical advancement has, however, been hindered by severe adverse effects due to systemic activation of the immune system. Liposomal drug delivery systems may modify biodistribution, cellular uptake, and extend blood circulation, and thus, potentially enable systemic administration of TLR agonists at therapeutic doses.

Sulochrins and alkaloids from a fennel endophyte sp. FVL2.

The fungal endophyte sp. strain FVL2, isolated from the traditional medicinal fennel plant, , was investigated for secondary metabolites. Fermentation on rice medium followed by chromatographic separation delivered three new natural products, 7-demethyl-neosulochrin (), fumigaclavine I () and -benzoyl-tryptophan () together with further 14 known metabolites, 1--methyl-sulochrin-4'-sulfate, questin, laccaic acid, isorhodoptilometrin, fumigaclavine A, fumigaclavine C, fumitremorgin C, fumigaquinazoline C, tryptoquivaline J, trypacidin, 3'--demethyl-sulochrin, 1--methyl-sulochrin, protocatechuic acid, and vermelone.