Spleen SORT LNP Generated in situ CAR T Cells Extend Survival in a Mouse Model of Lymphoreplete B Cell Lymphoma

Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B-cell lymphoma (BL). However, the current method of CAR T cell production is complicated and expensive, requiring collection of patient blood to enrich the T cell population, ex vivo engineering/activation, and quality assessment before the patient can receive the treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) to produce CAR T cells in situ and bypass the extensive and laborious process currently used. Optimized Spleen SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, and CD4+ T cells in wild-type mice. Spleen SORT LNPs delivered Cre recombinase mRNA and CAR encoding mRNA to T cells in reporter mice and in a lymphoreplete B cell lymphoma model (respectively) after intravenous injection without the need for active targeting ligands. Moreover, in situ CAR T cells increased the overall survival of mice with a less aggressive form of B cell lymphoma. In addition, in situ transfected CAR T cells reduced tumor metastasis to the liver by increasing tumor infiltrating lymphocytes. Overall, these results offer a promising alternative method for CAR T cell production with pre-clinical potential to treat hematological malignancies.     

Kinetics of the Anionic Polymerization of Buta‐1,3‐diene Considering Different Reactivities of the cis,trans and vinyl Structural Units

The anionic solution polymerization of buta‐1,3‐diene was modeled, considering the reactivity of the active sites to be different due to varying geometric configurations. With the first‐order Markov model, expressions for the fraction of active sites and dyad distribution were obtained. The rate constants were determined by fitting to the conversion and dyad experimental data using the nonlinear least squares method. The kinetic model shows that the microstructure and the dyads do not depend on initiator and butadiene concentration but only on rate constants. Without a modifier, the butadiene addition mechanism is entropic; with a modifier, the mechanism changes to entropic‐enthalpic.

     

Synthesis and structural characterization of diorganotin dithiocarbamates from 4‐(ethylaminomethyl)pyridine

Three 4‐(ethylaminodithiocarbamate) methylpyridine diorganotin derivatives were prepared using a one‐pot synthetic procedure from 4‐(ethylaminomethyl)pyridine, carbon disulfide, KOH as a base, and the corresponding diorganotin dichloride (R = Me, nBu, Ph). All three compounds were successfully characterized in solution (¹H, ¹³C, and ¹¹⁹Sn NMR) as well as in the solid state (IR, mass spectrometry, and X‐ray diffraction). In all three cases, an anisobidentate coordination mode was observed for the dithiocarbamate moiety to the tin atom, evidenced mainly by the different Sn S bond distances obtained from the X‐ray diffraction analysis. The organic groups attached to the tin atom have no influence on the reaction course, leading in each case to the formation of mononuclear complexes with the metal center in a hexacoordinated environment. Interestingly, in the solid state the methyl‐tin derivative showed Pyċn and SċSn intermolecular interactions, which were not observed in the two other complexes. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:422–428, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21032     

Synthesis of acetimino complexes of Pt(II) and Pt(IV) and the first heteronuclear mu-acetimido complexes

The reactions of [Ag(NH=CMe2)2]ClO4 with cis-[PtCl2L2] in a 1:1 molar ratio give cis-[PtCl(NH=CMe2)(PPh3)2]ClO4 (1cis) or cis-[PtCl(NH=CMe2)2(dmso)]ClO4 (2), and in 2:1 molar ratio, they produce [Pt(NH=CMe2)2L2](ClO4)2 [L = PPh3 (3), L2= tbbpy = 4,4'-di-tert-butyl-2,2'-dipyridyl (4)]. Complex 2 reacts with PPh3 (1:2) to give trans-[PtCl(NH=CMe2)(PPh3)2]ClO(4) (1trans). The two-step reaction of cis-[PtCl2(dmso)2], [Au(NH=CMe2)(PPh3)]ClO4, and PPh3 (1:1:1) gives [SP-4-3]-[PtCl(NH=CMe2)(dmso)(PPh3)]ClO4 (5). The reactions of complexes 2 and 4 with PhICl2 give the Pt(IV) derivatives [OC-6-13]-[PtCl3(NH=CMe2)(2)(dmso)]ClO4 (6) and [OC-6-13]-[PtCl2(NH=CMe2)2(dtbbpy)](ClO4)2 (7), respectively. Complexes 1cis and 1trans react with NaH and [AuCl(PPh3)] (1:10:1.2) to give cis- and trans-[PtCl{mu-N(AuPPh3)=CMe2}(PPh3)2]ClO4 (8cis and 8trans), respectively. The crystal structures of 4.0.5Et2O.0.5Me2CO and 6 have been determined; both exhibit pseudosymmetry.     

Dynamic mechanical analysis of thermotropic copolyester—short glass fiber composites

The influence of short glass fibers (SGF) on the dynamic mechanical properties and microstructure of thermotropic copolyesters based on 1,4‐hydroxybenzoic acid and 2,6‐hydroxynaphthoic acid (denoted B‐N) has been investigated. The mechanical relaxations of the reinforced B‐N/SGF composites were studied under torsion mode and the results were correlated with the degree of molecular alignment and degree of crystallinity as revealed by wide‐angle X‐ray scattering (WAXS). Addition of SGFs to B‐N liquid crystalline polymer (LCP) produced an increase in the solid‐to‐nematic transition temperature as well as an increase in the decomposition temperatures. Dynamic mechanical analysis (DMA) showed that the local motions associated with the β‐transition (∼61°C) are enhanced as the frequency of oscillation increases, i.e. the tan δ maximum increases at higher frequencies. On the other hand, the cooperative motions associated with the α‐transition (∼100°C) are decreased at higher frequencies. The addition of SGF reduced significantly the strength of the α‐transition. Thus, the cooperative molecular motions involving segments of the molecular chains associated with the α‐transition were compromised by the presence of SGFs resulting in an increase of the storage modulus, melting, and degradation temperatures. X‐ray scattering showed that the SGFs disrupted the degree of molecular alignment (as quantified by the order parameter ), , and the degree of crystallinity in the composites decreased as the concentration of SGFs increased. Thus, it is suggested that the increase in storage modulus in the composites is attributed to the contribution of the SGFs. Copyright © 2008 John Wiley & Sons, Ltd.     

Cover Picture: Microcontainers with Fluorescent Anisotropic Zeolite L Cores and Isotropic Silica Shells (Angew. Chem. Int. Ed. 7/2009)

Nanocontainers composed of zeolite L crystals were filled with fluorescent dyes and used as the core of a silica “box‐in‐a‐box” construction as in Russian matryoshka dolls, as described by A. Guerrero‐Martínez, L. de Cola, and co‐workers in their Communication on page 1266 ff. The anisotropic cores and isotropic shells of the multicolor emitting systems are separated by a polyelectrolyte layer and can be addressed independently. This approach opens fascinating routes for the construction of multifunctional nanosystems.

     

Surface‐enhanced Raman scattering of hydroxyproline

Surface‐enhanced Raman scattering (SERS) spectra of hydroxyproline and one deuterated analogue are reported. In this work, we tackled the problem of SERS reproducibility by employing gold colloids instead of the usual silver sols to achieve plasmon enhanced Raman scattering. We slightly modified modified a previously published procedure to obtain to obtain the colloid, and concentrated the gold particles by centrifugation. The SERS spectra show distinctive bands of hydroxyproline, assigned by comparison to normal Raman spectra and density functional theory calculations. Repeated measurements using this procedure showed reproducible SERS spectra. Copyright © 2011 John Wiley & Sons, Ltd.     

An investigation of hemibenzopinacolate radicals used in the synthesis of block-copolymers: ESR measurements and semiempirical calculations

Hemibenzopinacolate radicals may be incorporated in a polymer chain and the latter used as a macromolecular initiator. Kinetics of polymerization are strongly dependent on the substitution of the pinacolate. A large family of substituted (CH₃)₃SiOC(C₆H₅)₂ radicals has been synthesized and studied by electron spin resonance (ESR) and semiempirical molecular orbital calculations. ESR spectra are well resolved and, except for one derivative, allow an unambiguous determination of the hyperfine coupling splitting (HFS) constants. The ground state properties have been calculated within different approximations, namely MNDO, AM1 and PM3 for the geometry optimization and INDO for spin density. Geometries obtained within AM1 and PM3 approximations are satisfactory. The HFS constants evaluated using McConnell type relations and spin densities are in a quite good agreement with the experimental ones. It turns out that the effect of substitution on kinetics of polymerization cannot be attributed to any drastic change in the charge distribution.     

Electrical Resistivity and Thermally Stimulated Current in CuIn5Se8

From electrical resistivity measurements in the range from 240 to 450 K and from optical absorption measurements the energy gap value of CuIn₅Se₈ has been found to be 1.13 eV. Thermally stimulated current and electrical measurements at high temperature performed in indium annealed samples show deep levels at 0.55 and 0.79 eV, respectively. These defects are expected to be associated with interstitial indium or indium in copper site because of the In‐rich condition.