Cu tumor labeling with hexadentate picolinic acid-based bispidine immunoconjugates.

Discussed are two picolinate appended bispidine ligands (3,7-diazabicyclo[3.3.1]nonane derivatives) in comparison with an earlier described bis-pyridine derivative, which are all known to strongly bind Cu.

Immunotheranostic target modules for imaging and navigation of UniCAR T-cells to strike FAP-expressing cells and the tumor microenvironment.

Background: Chimeric antigen receptor (CAR) T-cells are a promising approach in cancer immunotherapy, particularly for treating hematologic malignancies. Yet, their effectiveness is limited when tackling solid tumors, where immune cell infiltration and immunosuppressive tumor microenvironments (TME) are major hurdles. Fibroblast activation protein (FAP) is highly expressed on cancer-associated fibroblasts (CAFs) and various tumor cells, playing an important role in tumor growth and immunosuppression.

Methods gold standard in clinic millifluidics multiplexed extended gate field-effect transistor biosensor with gold nanoantennae as signal amplifiers.

We present a portable multiplexed biosensor platform based on the extended gate field-effect transistor and demonstrate its amplified response thanks to gold nanoparticle-based bioconjugates introduced as a part of the immunoassay. The platform comprises a disposable chip hosting an array of 32 extended gate electrodes, a readout module based on a single transistor operating in constant charge mode, and a multiplexer to scan sensing electrodes one-by-one. Although employing only off-the-shelf electronic components, our platform achieves sensitivities comparable to fully customized nanofabricated potentiometric sensors.

Exploring the Potential of Nanogels: From Drug Carriers to Radiopharmaceutical Agents.

Nanogels open up access to a wide range of applications and offer among others hopeful approaches for use in the field of biomedicine. This review provides a brief overview of current developments of nanogels in general, particularly in the fields of drug delivery, therapeutic applications, tissue engineering, and sensor systems. Specifically, cyclodextrin (CD)-based nanogels are important because they have exceptional complexation properties and are highly biocompatible.

Bispidine Chelators for Radiopharmaceutical Applications with Lanthanide, Actinide, and Main Group Metal Ions.

Octadentate and specifically nonadentate ligands with a bispidine scaffold (3,7-diazabicyclo[3.3.1]nonane) are known to be efficiently coordinated to a range of metal ions of interest in radiopharmaceutical chemistry and lead to exceedingly stable and inert complexes.

Specific and safe targeting of glioblastoma using switchable and logic-gated RevCAR T cells.

Glioblastoma (GBM) is still an incurable tumor that is associated with high recurrence rate and poor survival despite the current treatment regimes. With the urgent need for novel therapeutic strategies, immunotherapies, especially chimeric antigen receptor (CAR)-expressing T cells, represent a promising approach for specific and effective targeting of GBM. However, CAR T cells can be associated with serious side effects.

Toward Personalized Medicine: One Chelator for Imaging and Therapy with Lutetium-177 and Actinium-225.

We report a nonadentate bispidine (3,7-diazabicyclo[3.3.1]nonane) that unveils the potential to bind theranostically relevant radionuclides, including indium-111, lutetium-177, and actinium-225 under mild labeling conditions.

Switching on Cytotoxicity of Water-Soluble Diiron Organometallics by UV Irradiation.

The diiron compounds [FeCp(CO)(μ-CO)(μ-CSEt)]CFSO, []CFSO, K[FeCp(CO)(CNCHCO)], K[], [FeCp(CO)(μ-CO)(μ-CNMe)]NO, []NO, [FeCp(CO)(PTA){μ-CNMe(Xyl)}]CFSO, []CFSO, and [FeCp(CO)(μ-CO){μ-η:η-C(4-CHCOH)CHCNMe}]CFSO, []CFSO, containing a bridging carbyne, isocyanoacetate, or vinyliminium ligand, were investigated for their photoinduced cytotoxicity. Specifically, the novel water-soluble compounds K[], []NO, and []CFSO were synthesized and characterized by elemental analysis and IR and multinuclear NMR spectroscopy. Stereochemical aspects concerning []CFSO were elucidated by H NOESY NMR and single-crystal X-ray diffraction.

Metal ion size profoundly affects Hglyox chelate chemistry.

The bisoxine hexadentate chelating ligand, Hglyox was investigated for its affinity for Mn, Cu and Lu ions; all three metal ions are relevant with applications in nuclear medicine and medicinal inorganic chemistry. The aqueous coordination chemistry and thermodynamic stability of all three metal complexes were thoroughly investigated by detailed DFT structure calculations and stability constant determination, by employing UV in-batch spectrophotometric titrations, giving pM values (pM = -log[M ] when [M ] = 1 μM, [L] = 10 μM at pH 7.4 and 25 °C) - pCu (25.

Dual-Labelling Strategies for Nuclear and Fluorescence Molecular Imaging: Current Status and Future Perspectives.

Molecular imaging offers the possibility to investigate biological and biochemical processes non-invasively and to obtain information on both anatomy and dysfunctions. Based on the data obtained, a fundamental understanding of various disease processes can be derived and treatment strategies can be planned. In this context, methods that combine several modalities in one probe are increasingly being used.

Bis(amido)bis(oxinate)diamine Ligands for theranostic radiometals.

With the interest in radiometal-containing diagnostic and therapeutic pharmaceuticals increasing rapidly, appropriate ligands to coordinate completely and stably said radiometals is essential. Reported here are two novel, bis(amido)bis(oxinate)diamine ligands, Hamidohox (2,2'-(ethane-1,2-diylbis(((8-hydroxyquinolin-2-yl)methyl)azanediyl))diacetamide) and HamidoC3hox (2,2'-(propane-1,3-diylbis(((8-hydroxyquinolin-2-yl)methyl)azanediyl))diacetamide), that combine two 8-hydroxyquinoline and amide donor groups and differ by one carbon in their 1,2-ethylenediamine vs. 1,3-diaminopropane backbones, respectively.

Hpyhox - Octadentate Bis(pyridyloxine).

A new versatile chelating ligand for intermediate size and softness radiometals [Cu]Cu and [In]In, Hpyhox, was synthesized by introducing pyridine as a new donor moiety to complement 8-hydroxyquinoline on an ethylenediamine backbone. The combination of pyridine and oxine as donor sets was explored through structural analysis, and crystals of the three metal complexes with Cu, La, and In demonstrate how the ligand adapts to accommodate metal ions of different sizes and charge. Exhaustive in-batch UV solution studies characterized the protonation constants of the free ligand as well as the formation constants of the metal complexes with Cu, In, and La.

High denticity oxinate-linear-backbone chelating ligand for diagnostic radiometal ions [In]In and [Zr]Zr.

Advances in nuclear medicine depend on chelating ligands that form highly stable and kinetically inert complexes with relevant radiometal ions for use in diagnosis or therapy. A new potentially decadentate ligand, Hdecaox, was synthesised to incorporate two 8-hydroxyquinoline moieties on either end of a diethylenetriamine backbone decorated with three carboxylic acids, one at each N atom of the backbone. Metal complexation was assessed using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS) with In, Zr and La.

Light-Activated Carbon Monoxide Prodrugs Based on Bipyridyl Dicarbonyl Ruthenium(II) Complexes.

Two photoactivatable dicarbonyl ruthenium(II) complexes based on an amide-functionalised bipyridine scaffold (4-position) equipped with an alkyne functionality or a green-fluorescent BODIPY (boron-dipyrromethene) dye have been prepared and used to investigate their light-induced decarbonylation. UV/Vis, FTIR and C NMR spectroscopies as well as gas chromatography and multivariate curve resolution alternating least-squares analysis (MCR-ALS) were used to elucidate the mechanism of the decarbonylation process. Release of the first CO molecule occurs very quickly, while release of the second CO molecule proceeds more slowly.

Rapid Thermodynamically Stable Complex Formation of [In]In, [Y]Y, and [Lu]Lu with Hdappa.

A phosphinate-bearing picolinic acid-based chelating ligand (Hdappa) was synthesized and characterized to assess its potential as a bifunctional chelator (BFC) for inorganic radiopharmaceuticals. Nuclear magnetic resonance (NMR) spectroscopy was employed to investigate the chelator coordination chemistry with a variety of nonradioactive trivalent metal ions (In, Lu, Y, Sc, La, Bi). Density functional theory (DFT) calculations explored the coordination environments of aforementioned metal complexes.

Chelation in One Fell Swoop: Optimizing Ligands for Smaller Radiometal Ions.

[Sc]Sc, [Ga]Ga, and [In]In are the three most attractive trivalent smaller radiometalnuclides, offering a wide range of distinct properties (emission energies and types) in the toolbox of nuclear medicine. In this study, all three of the metal ions are successfully chelated using a new oxine-based hexadentate ligand, Hglyox, which forms thermodynamically stable neutral complexes with exceptionally high pM values [pIn (34) > pSc (26) > pGa (24.9)].

Synthesis, structural characterisation, and cytotoxicity studies of Bi, W, and Mo containing homo- and hetero-bimetallic polyoxometalates.

Three new and different homo- and hetero-bimetallic polyoxometalate (POM) species have been synthesised by simple one-pot synthetic methods utilising naturally occurring bismite (BiO) (or Bi(NO)·5HO) and aryl sulfonic acids. The POM species isolated are (NH)[BiWO]·14HO (1·14HO), (NH)[Bi(DMSO)][MoO]·HO (2·HO) and [(NH)(MoO(OH)·16HO)]·45HO (3·45HO). The compounds have been characterised by X-ray crystallography, energy dispersive X-ray spectroscopy (EDX), powdered X-ray diffraction (PXRD), mass spectrometry (ESI-MS), Raman spectroscopy, thermogravimetric (TGA) and ICP analyis.

Synthesis, Structural Characterization and Photodecarbonylation Study of a Dicarbonyl Ruthenium(II)-Bisquinoline Complex.

A photoactivatable ruthenium(II) carbonyl complex -[Ru(II)Cl(BisQ)(CO)]PF was prepared using a tridentate bisquinoline ligand (BisQ=(2,6-diquinolin-2-yl)pyridin). Compound was thoroughly characterized by standard analytical methods and single crystal X-ray diffraction. The crystal structure of the complex cation reveals a distorted octahedral geometry.

Harnessing the Coordination Chemistry of 1,4,7-Triazacyclononane for Biomimicry and Radiopharmaceutical Applications.

1,4,7-Triazacyclononane (TACN)-based mono- and poly-nuclear metal complexes have found extensive use as biological mimics for understanding the structural and operational aspects of complex natural systems. Their coordination flexibility has also provided researchers access to a vast library of radiometal-binding motifs that display excellent thermodynamic stability and kinetic inertness upon metal complexation. Synthetic modification of the TACN backbone has yielded ligands that can form metal complexes with coordination geometries well suited for these applications.

Facile preparation of multifunctionalisable 'stealth' upconverting nanoparticles for biomedical applications.

Pure hexagonal (β-phase) NaYF-based hydrophobic upconverting nanoparticles (UCNPs) were surface-modified with O-phospho-l-threonine (OPLT), alendronic acid, and PEG-phosphate ligands to generate water-dispersible UCNPs. Fourier-transform infrared (FTIR) spectroscopy was used to establish the presence of the ligands on the UCNP surface. These UCNPs exhibit great colloidal stability and a near-neutral surface at physiological pH, as confirmed by dynamic light scattering (DLS) and zeta potential (ζ) measurements, respectively.

Distribution and kinetics of the Kv1.3-blocking peptide HsTX1[R14A] in experimental rats.

The peptide HsTX1[R14A] is a potent and selective blocker of the voltage-gated potassium channel Kv1.3, which is a highly promising target for the treatment of autoimmune diseases and other conditions. In order to assess the biodistribution of this peptide, it was conjugated with NOTA and radiolabelled with copper-64.

Studies of Carbon Monoxide Release from Ruthenium(II) Bipyridine Carbonyl Complexes upon UV-Light Exposure.

The UV-light-induced CO release characteristics of a series of ruthenium(II) carbonyl complexes of the form trans-Cl[RuLCl(CO)] (L = 4,4'-dimethyl-2,2'-bipyridine, 4'-methyl-2,2'-bipyridine-4-carboxylic acid, or 2,2'-bipyridine-4,4'-dicarboxylic acid) have been elucidated using a combination of UV-vis absorbance and Fourier transform infrared spectroscopies, multivariate curve resolution alternating least-squares analysis, and density functional theory calculations. In acetonitrile, photolysis appears to proceed via a serial three-step mechanism involving the sequential formation of [RuL(CO)(CHCN)Cl], [RuL(CHCN)Cl], and [RuL(CHCN)Cl]. Release of the first CO molecule occurs quickly (k ≫ 3 min), while release of the second CO molecule proceeds at a much more modest rate (k = 0.

Comprehensive Vibrational Spectroscopic Investigation of trans,trans,trans-[Pt(N3)2(OH)2(py)2], a Pt(IV) Diazido Anticancer Prodrug Candidate.

We report a detailed study of a promising photoactivatable metal-based anticancer prodrug candidate, trans,trans,trans-[Pt(N3)2(OH)2(py)2] (C1; py = pyridine), using vibrational spectroscopic techniques. Attenuated total reflection Fourier transform infrared (ATR-FTIR), Raman, and synchrotron radiation far-IR (SR-FIR) spectroscopies were applied to obtain highly resolved ligand and Pt-ligand vibrations for C1 and its precursors (trans-[Pt(N3)2(py)2] (C2) and trans-[PtCl2(py)2] (C3)). Distinct IR- and Raman-active vibrational modes were assigned with the aid of density functional theory calculations, and trends in the frequency shifts as a function of changing Pt coordination environment were determined and detailed for the first time.

Bispidine dioxotetraaza macrocycles: a new class of bispidines for (64)Cu PET imaging.

The three new dioxo-tetraazamacrocyclic ligands with a fused, very rigid bispidine (3,7-diazabicyclo[3.3.1]nonane) group connecting the two tertiary amine donors, and ethyl, propyl, or benzene groups connecting the two amide donors are highly preorganized and lead to very stable, uncharged Cu(II) complexes.