Hydrosulphide-methaemoglobin-albumin cluster: a hydrogen sulphide donor.

Methaemoglobin (metHb) possesses inherent characteristics that facilitate reversible binding to hydrogen sulphide. Exogenous hydrogen sulphide supplementation imparts beneficial bioactive effects, including antioxidant and anti-inflammatory; hence, we hypothesized that the metHb-hydrogen sulphide complex could act as a hydrogen sulphide donor for medication. In this study, we prepared a hydrosulphide-metHb-albumin (HS-metHb-albumin) cluster and examined its applicability as a hydrogen sulphide donor in the mice model of hepatic ischemia-reperfusion injury.

Transport of Zinc-Phthalocyanine to Cancer Cells Using Myoglobin-Albumin Fusion Protein for Photodynamic Therapy.

Photodynamic therapy (PDT) is a noninvasive approach to cancer treatment, wherein cell death is initiated by singlet oxygen (O) production via energy transfer from excited photosensitizers to ground-state O. Effective clinical photosensitizers necessitate water solubility for in vivo administration. Hydrophobic dyes, such as phthalocyanines, cannot be used directly as photosensitizers.

Dual delivery of carbon monoxide and doxorubicin using haemoglobin-albumin cluster: proof of concept for well-tolerated cancer therapy.

A serious concern of doxorubicin (DOX) therapy is that it causes severe adverse effects, particularly cardiotoxicity. Carbon monoxide (CO) possesses powerful cytoprotective effects against drug-induced organ injury and is expected to ameliorate DOX-induced cardiotoxicity. In this study, a dual carrier of DOX and CO (CO-HemoAct-DOX) was fabricated based on a haemoglobin-albumin cluster (HemoAct), which is a protein cluster with a haemoglobin core structure wrapped by serum albumin.

Zinc-Substituted Hemoglobin-Albumin Cluster as a Porphyrin-Carrier for Enhanced Photodynamic Therapy.

Apohemoprotein is focused on the field of theranostics, serving as a porphyrin carrier. Hemoglobin (Hb) consists of αβ tetramer with iron(II)-protoporphyrin IX (heme) bound to each globin. However, heme-removed Hb (apoHb) causes dissociation at αβ interfaces and aggregation under physiological conditions.

Polyoxazoline-Conjugated l-Asparaginase: An Antibody-Production-Free Therapeutic Agent for Acute Lymphoblastic Leukemia.

l-asparaginase (ASNase), an enzyme that catalyzes the hydrolysis of l-asparagine into l-aspartic acid, is frequently used as a medication for acute lymphoblastic leukemia (ALL). However, when derived from bacterial sources, this enzyme can elicit side effects, including allergic or hypersensitivity reactions, owing to immune responses. Here, we describe the synthesis of polyoxazoline-conjugated ASNase (POx-ASNase) and investigate its enzyme activity, anticancer efficacy, immunogenicity, and retention in the bloodstream.

Protein-Porphyrin Complex Photosensitizers for Anticancer and Antimicrobial Photodynamic Therapies.

Photodynamic therapy (PDT) efficiently induces apoptosis through visible-light irradiation of photosensitizers (PSs) within tumors and microbial cells. Porphyrin analogues serve as widely utilized photosensitizing agents with their therapeutic abilities being governed by molecular structures and central metal ions. However, these macrocyclic compounds tend to agglutinate and form stacks in aqueous environments, resulting in a loss of photochemical activity.

Neuroprotective effects of a hemoglobin-based oxygen carrier (stroma-free hemoglobin nanoparticle) on ischemia reperfusion injury.

The application of hemoglobin (Hb)-based oxygen carriers (HBOCs) to the treatment of cerebral ischemia has been investigated. A cluster of 1 Hb and 3 human serum albumins (Hb-HSA) was found to exert neuroprotective effects on ischemia/reperfusion injury. Stroma-free hemoglobin nanoparticles (SFHbNP), a subsequently developed HBOC consisting of a spherical polymerized stroma-free Hb core with a HSA shell, contains the natural antioxidant enzyme catalase and, thus, is expected to exert additive effects.

Pharmaceutical stability of methemoglobin-albumin cluster as an antidote for hydrogen sulfide poisoning after one-year storage in freeze-dried form.

Long-term stability during storage is an important requirement for pharmaceutical preparations. The methemoglobin (metHb)-albumin cluster, in which bovine metHb is covalently enveloped with an average of three human albumin molecules, is a promising antidote for hydrogen sulfide (HS) poisoning. In this study, we investigated the pharmaceutical stability of metHb-albumin cluster after storage for one year in solution and as freeze-dried powder.

Poly(2-ethyl-2-oxazoline)-Conjugated Hemoglobins as a Red Blood Cell Substitute.

Hemoglobin wrapped covalently with poly(2-ethyl-2-oxazoline)s (POx-Hb) is characterized physicochemically and physiologically as an artificial O carrier for use as a red blood cell (RBC) substitute. The POx-Hb is generated by linkage of porcine Hb surface-lysines to a sulfhydryl terminus of the POx derivative, with the average binding number of the polymers ascertained as 6. The POx-Hb shows moderately higher colloid osmotic activity and O affinity than the naked Hb.

Pharmaceutical Integrity of Lyophilized Methemoglobin-Albumin Clusters after Reconstitution.

Covalent attachment of a ferric hemoglobin (metHb) core to three human serum albumin molecules to form metHb-albumin clusters has previously been used to develop an antidote for hydrogen sulfide poisoning. Lyophilization is one of the most effective approaches to preserve protein pharmaceuticals with minimum contamination and decomposition. However, there is concern that lyophilized proteins may undergo pharmaceutical alteration on reconstitution.

Polyoxazoline-conjugated porcine serum albumin as an artificial plasma expander for dogs.

Veterinary medicine has made tremendous progress for domestic dogs, which are irreplaceable family members enriching human life. Nevertheless, no adequate supply system exists for their blood products. This study examined the synthesis, structure, safety, and efficacy of poly(2-ethyl-2-oxazoline)-conjugated porcine serum albumin (POx-PSA) as an artificial plasma expander for dogs.

Methemoglobin-albumin clusters for cyanide detoxification.

Sodium nitrite (NaNO) is a universal antidote for patients with cyanide poisoning. However, its use has serious drawbacks in terms of efficacy and safety. Herein, we present a promising antidote: methemoglobin (metHb)-albumin clusters.

Zinc Substituted Myoglobin-Albumin Fusion Protein: A Photosensitizer for Cancer Therapy.

Myoglobin combined with human serum albumin (Mb-HSA) can be produced using yeast Pichia pastoris as a host strain, with secretion into the culture medium. This Mb-HSA fusion protein possesses identical O binding affinity to that of naked Mb. The Mb unit is reconstituted with a zinc(II) protoporphyrin IX, yielding (zinc substituted Mb)-HSA, ZnMb-HSA.

Core-Shell Structured Hemoglobin Nanoparticles as Artificial O Carriers.

This paper describes the synthesis and O binding properties of core-shell structured hemoglobin (Hb) nanoparticles (NPs), artificial O carriers of five types, as designed for use as red blood cell (RBC) substitutes. Human adult Hbs were polymerized using α-succinimidyl-ω-maleimide and dithiothreitol in spheroidal shapes to create parent particles. Subsequent covalent wrapping of the sphere with human serum albumin (HSA) yielded 100 nm-diameter Hb nanoparticles (HbNPs).

Methemoglobin-albumin clusters for the treatment of hydrogen sulfide intoxication.

Hydrogen sulfide (HS) has attracted significant attention as a seed in drug development. However, HS is toxic and induces lethal acute intoxication. Here, we developed methemoglobin (metHb)-albumin clusters as detoxifying agents for HS intoxication, which were designed based on the inherent binding property of metHb with HS.

Hemoglobin-albumin clusters as an artificial O carrier: Physicochemical properties and resuscitation from hemorrhagic shock in rats.

A bovine hemoglobin (HbBv) or human adult hemoglobin (HbA) wrapped covalently by human serum albumins (HSAs), hemoglobin-albumin clusters (HbBv-HSA and HbA-HSA ), are artificial O carriers used as a red blood cell substitute. This article describes the physicochemical properties of the HbBv-HSA and HbA-HSA solutions, and their abilities to restore the systemic condition after resuscitation from hemorrhagic shock in anesthetized rats. The HbBv-HSA and HbA-HSA , which have high colloid osmotic activity, showed equivalent solution characteristics and O binding parameters.

Polyelectrolyte/Gold Nanoparticle Nanotubes Incorporating Doxorubicin-Loaded Liposomes.

Anticancer agent doxorubicin-loaded liposomes (DoxLs) were drawn spontaneously into nanotubes comprising multilayers of polyelectrolytes and gold nanoparticles (PAuNTs). We describe a unique structure of PAuNTs incorporating DoxLs (DoxL-PAuNT). The number of DoxLs adsorbed on the tube interior surface was ascertained as 2.

Genetically and chemically tuned haemoglobin-albumin trimers with superior O transport efficiency.

Haemoglobin (Hb)-albumin (HSA) trimers were synthesized using five distinct Hb variants in which the structures were genetically and chemically tuned as an artificial O carrier and used as a red blood cell (RBC) substitute. The trimers were found to have moderately low O affinity ( = 23-34 Torr, 37 °C) and high co-operativity, yielding a maximum O transport efficiency 1.8-fold higher than that of human RBCs.

Haemoglobin(βK120C)-albumin trimer as an artificial O carrier with sufficient haemoglobin allostery.

The allosteric O release of haemoglobin (Hb) allows for efficient O delivery from the lungs to the tissues. However, allostery is weakened in Hb-based O carriers because the chemical modifications of the Lys- and Cys-β93 residues prevent the quaternary transition of Hb. In this paper, we describe the synthesis and O binding properties of a recombinant Hb [rHb(βK120C)]-albumin heterotrimer that maintains sufficient Hb allostery.

Methemoglobin-Albumin Cluster Incorporating Protoporphyrin IX: Dual Functional Protein Drug for Photodynamic Therapy.

We describe the synthesis, photophysical properties, and photodynamic activity of a methemoglobin (metHb) wrapped covalently by human serum albumins (HSAs) incorporating protoporphyrin IX (PPIX): a metHb-HSA -PPIX cluster. The metHb core catalyzes H O disproportionation to generate O in tumor tissue. The HSA -PPIX shell acts as a photosensitizer for O formation.

Acid-Mediated Sulfonylthiolation of Arenes via Selective Activation of Morpholino Dithiosulfonate.

A trifluoroacetic-acid-mediated desulfurilative sulfonylthiolation of arenes using -morpholino dithiosulfonate is described. This system is based on selective activation of the morpholino group over the tosyl group of the doubly transformable sulfur surrogate. Mechanistic studies suggested that the reaction proceeds through electrophilic aromatic substitution followed by sulfur extrusion.

Supramolecular linear coordination polymers of human serum albumin and haemoglobin.

We describe the synthesis, structure, and functionalities of water-soluble linear coordination polymers of human serum albumin and haemoglobin, which are connected via a bis(terpyridyl)-Fe complex. These protein fibres were self-assembled by lyophilisation and were transformed into single-wall nanotubes. The biological activities of the protein units were perfectly preserved in the long fibres.

Lewis acid-base synergistic catalysis of cationic halogen-bonding-donors with nucleophilic counter anions.

Cationic halogen-bonding-donors with little or non-coordinating counter anions have attracted great attention as new Lewis acid type organocatalysts. However, these anions cannot function as nucleophilic activation sites due to their low Lewis basicity. In this study, 1,3,4-triaryl-5-iodotriazolium iodides have been developed as bifunctional catalysts for simultaneous activation of nucleophiles and electrophiles.

Rectangular Holes in Porphyrin Isomers Act As Mono- and Binucleating Ligands: Stereochemistry of Mono- and Diboron Porphycenes and Their Protonation Behaviors.

The first boron complexes of porphycenes, structural isomers of porphyrin, are reported. They are synthesized in good yields by reacting the free-base porphycene ligands with BF·EtO through a microwave-assisted method. Depending on the substituent group of porphycenes, two different coordination structures, mono- and diboron porphycenes, are obtained simultaneously.