Branched amphiphilic peptide capsules: Cellular uptake and retention of encapsulated solutes

Branched amphiphilic peptide capsules (BAPCs) are peptide nanospheres comprised of equimolar proportions of two branched peptide sequences bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK that self-assemble to form bi-layer delimited capsules. In two recent publications we described the lipid analogous characteristics of our BAPCs, examined their initial assembly, mode of fusion, solute encapsulation, and resizing and delineated their capability to be maintained at a specific size by storing them at 4 °C. In this report we describe the stability, size limitations of encapsulation, cellular localization, retention and, bio-distribution of the BAPCs in vivo. The ability of our constructs to retain alpha particle emitting radionuclides without any apparent leakage and their persistence in the peri-nuclear region of the cell for extended periods of time, coupled with their ease of preparation and potential tune-ability, makes them attractive as biocompatible carriers for targeted cancer therapy using particle emitting radioisotopes. This article is part of a Special Issue entitled: Interfacially active peptides and proteins

Tris‐{hydridotris(1‐pyrazolyl)borato}actinide Complexes: Synthesis, Spectroscopy, Crystal Structure, Bonding Properties and Magnetic Behaviour

The isostructural compounds of the trivalent actinides uranium, neptunium, plutonium, americium, and curium with the hydridotris(1-pyrazolyl)borato (Tp) ligand An[η$_{3}$-HB(N$_{2}$C$_{3}$H$_{3}$)$_{3}$]$_{3}$ (AnTp$_{3}$) have been obtained through several synthetic routes. Structural, spectroscopic (absorption, infrared, laser fluorescence) and magnetic characterisation of the compounds were performed in combination with crystal field, density functional theory (DFT) and relativistic multiconfigurational calculations. The covalent bonding interactions were analysed in terms of the natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) models

Tris‐{hydridotris(1‐pyrazolyl)borato}actinide Complexes: Synthesis, Spectroscopy, Crystal Structure, Bonding Properties and Magnetic Behaviour

The isostructural compounds of the trivalent actinides uranium, neptunium, plutonium, americium, and curium with the hydridotris(1-pyrazolyl)borato (Tp) ligand An[η$_{3}$-HB(N$_{2}$C$_{3}$H$_{3}$)$_{3}$]$_{3}$ (AnTp$_{3}$) have been obtained through several synthetic routes. Structural, spectroscopic (absorption, infrared, laser fluorescence) and magnetic characterisation of the compounds were performed in combination with crystal field, density functional theory (DFT) and relativistic multiconfigurational calculations. The covalent bonding interactions were analysed in terms of the natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) models

Targeted Killing of Virally Infected Cells by Radiolabeled Antibodies to Viral Proteins

BACKGROUND: The HIV epidemic is a major threat to health in the developing and western worlds. A modality that targets and kills HIV-1-infected cells could have a major impact on the treatment of acute exposure and the elimination of persistent reservoirs of infected cells. The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo. METHODS AND FINDINGS: Antibodies to HIV-1 envelope glycoproteins gp120 and gp41 labeled with radioisotopes bismuth 213 ((213)Bi) and rhenium 188 ((188)Re) selectively killed chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells (hPBMCs) in vitro. Treatment of severe combined immunodeficiency (SCID) mice harboring HIV-1-infected hPBMCs in their spleens with a (213)Bi- or (188)Re-labeled monoclonal antibody (mAb) to gp41 resulted in a 57% injected dose per gram uptake of radiolabeled mAb in the infected spleens and in a greater than 99% elimination of HIV-1-infected cells in a dose-dependent manner. The number of HIV-1-infected thymocytes decreased 2.5-fold in the human thymic implant grafts of SCID mice treated with the (188)Re-labeled antibody to gp41 compared with those treated with the (188)Re-control mAb. The treatment did not cause acute hematologic toxicity in the treated mice. CONCLUSIONS: The current study demonstrates the effectiveness of HIV-targeted radioimmunotherapy and may provide a novel treatment option in combination with highly active antiretroviral therapy for the eradication of HIV

Organometallic neptunium(III) complexes

Studies of transuranic organometallic complexes provide a particularly valuable insight into covalent contributions to the metal–ligand bonding, in which the subtle differences between the transuranium actinide ions and their lighter lanthanide counterparts are of fundamental importance for the effective remediation of nuclear waste. Unlike the organometallic chemistry of uranium, which has focused strongly on UIII and has seen some spectacular advances, that of the transuranics is significantly technically more challenging and has remained dormant. In the case of neptunium, it is limited mainly to NpIV. Here we report the synthesis of three new NpIII organometallic compounds and the characterization of their molecular and electronic structures. These studies suggest that NpIII complexes could act as single-molecule magnets, and that the lower oxidation state of NpII is chemically accessible. In comparison with lanthanide analogues, significant d- and f-electron contributions to key NpIII orbitals are observed, which shows that fundamental neptunium organometallic chemistry can provide new insights into the behaviour of f-elements