Biodegradable Metal Complex-Gated Organosilica for Dually Enhanced Chemodynamic Therapy through GSH Depletions and NIR Light-Triggered Photothermal Effects.

Hollow silica spheres have been widely studied for drug delivery because of their excellent biosecurity and high porosity. However, difficulties with degradation in the tumor microenvironment (TME) and premature leaking during drug delivery limit their clinical applications. To alleviate these problems, herein, hollow organosilica spheres (HOS) were initially prepared using a "selective etching strategy" and loaded with a photothermal drug: new indocyanine green (IR820). Then, the Cu2+-tannic acid complex (Cu-TA) was deposited on the surface of the HOS, and a new nanoplatform named HOS@IR820@Cu-TA (HICT) was finally obtained. The deposition of Cu-TA can gate the pores of HOS completely to prevent the leakage of IR820 and significantly enhance the loading capacity of HOS. Once in the mildly acidic TME, the HOS and outer Cu-TA decompose quickly in response, resulting in the release of Cu2+ and IR820. The released Cu2+ can react with the endogenous glutathione (GSH) to consume it and produce Cu+, leading to the enhanced production of highly toxic ·OH through a Fenton-like reaction due to the overexpressed H2O2 in the TME. Meanwhile, the ·OH generation was remarkably enhanced by the NIR light-responsive photothermal effect of IR820. These collective properties of HICT enable it to be a smart nanomedicine for dually enhanced chemodynamic therapy through GSH depletions and NIR light-triggered photothermal effects.

A Versatile Nanozyme-Based NADH Circulating Oxidation Reactor for Tumor Therapy through Triple Cellular Metabolism Disruption.

Nanozyme-based metabolic regulation triggered by tumor-specific endogenous stimuli has emerged as a promising therapeutic strategy for tumors. The current efficacy, however, is constrained by the limited concentration of endogenous substrates and the metabolic plasticity of tumors. Consequently, the implementation of efficient metabolic regulation in tumor therapy is urgently needed. Herein, a versatile nanozyme-based nicotinamide adenine dinucleotide (NADH) circulating oxidation nanoreactor is reported. First, the synthesized cobalt-doped hollow carbon spheres (Co-HCS) possess NADH oxidase (NOX)-mimicking activity for the NADH oxidation to disrupt oxidative phosphorylation (OXPHOS) pathway of tumor cells. Second, the substrate-cycle manner of Co-HCS can be used for NADH circulating oxidation to overcome the limitation of substrate deficiency. Finally, 2-Deoxy-D-glucose (2-DG) and 6-aminonicotinamide (6-AN) are introduced to block glycolysis and pentose phosphate pathway (PPP), thus creating a versatile nanozyme-based NADH circulating oxidation nanoreactor (Co-HCS/D/A) for tumor therapy through triple cellular metabolism disruption. In vitro and in vivo results demonstrate that the designed nanoreactor not only enhances the catalytic efficiency but also disrupts the tumor metabolic homeostasis, leading to efficient therapy outcome. This study develops a novel NADH circulating oxidation nanoreactor for tumor therapy through triple cellular metabolism disruption, which addresses the limitations of current nanozyme-based metabolism regulation for tumor therapy.

Systematic study and uncertainty evaluation of P, T-odd molecular enhancement factors in BaF.

A measurement of the magnitude of the electric dipole moment of the electron (eEDM) larger than that predicted by the Standard Model (SM) of particle physics is expected to have a huge impact on the search for physics beyond the SM. Polar diatomic molecules containing heavy elements experience enhanced sensitivity to parity (P) and time-reversal (T)-violating phenomena, such as the eEDM and the scalar-pseudoscalar (S-PS) interaction between the nucleons and the electrons, and are thus promising candidates for measurements. The NL-eEDM collaboration is preparing an experiment to measure the eEDM and S-PS interaction in a slow beam of cold BaF molecules [P. Aggarwal et al., Eur. Phys. J. D 72, 197 (2018)]. Accurate knowledge of the electronic structure parameters, Wd and Ws, connecting the eEDM and the S-PS interaction to the measurable energy shifts is crucial for the interpretation of these measurements. In this work, we use the finite field relativistic coupled cluster approach to calculate the Wd and Ws parameters in the ground state of the BaF molecule. Special attention was paid to providing a reliable theoretical uncertainty estimate based on investigations of the basis set, electron correlation, relativistic effects, and geometry. Our recommended values of the two parameters, including conservative uncertainty estimates, are 3.13 ±0.12×1024Hzecm for Wd and 8.29 ± 0.12 kHz for Ws.

Enhanced P,T-violating nuclear magnetic quadrupole moment effects in laser-coolable molecules.

Nuclear magnetic quadrupole moments (MQMs), such as intrinsic electric dipole moments of elementary particles, violate both parity and time-reversal symmetry and, therefore, probe physics beyond the standard model. We report on accurate relativistic coupled cluster calculations of the nuclear MQM interaction constants in BaF, YbF, BaOH, and YbOH. We elaborate on estimates of the uncertainty of our results. The implications of experiments searching for nonzero nuclear MQMs are discussed.

High accuracy theoretical investigations of CaF, SrF, and BaF and implications for laser-cooling.

The NL-eEDM collaboration is building an experimental setup to search for the permanent electric dipole moment of the electron in a slow beam of cold barium fluoride molecules [NL-eEDM Collaboration, Eur. Phys. J. D 72, 197 (2018)]. Knowledge of the molecular properties of BaF is thus needed to plan the measurements and, in particular, to determine the optimal laser-cooling scheme. Accurate and reliable theoretical predictions of these properties require the incorporation of both high-order correlation and relativistic effects in the calculations. In this work, theoretical investigations of the ground and lowest excited states of BaF and its lighter homologs, CaF and SrF, are carried out in the framework of the relativistic Fock-space coupled cluster and multireference configuration interaction methods. Using the calculated molecular properties, we determine the Franck-Condon factors (FCFs) for the A2Π1/2→X2Σ1/2 + transition, which was successfully used for cooling CaF and SrF and is now considered for BaF. For all three species, the FCFs are found to be highly diagonal. Calculations are also performed for the B2Σ1/2 +→X2Σ1/2 + transition recently exploited for laser-cooling of CaF; it is shown that this transition is not suitable for laser-cooling of BaF, due to the nondiagonal nature of the FCFs in this system. Special attention is given to the properties of the A'2Δ state, which in the case of BaF causes a leak channel, in contrast to CaF and SrF species where this state is energetically above the excited states used in laser-cooling. We also present the dipole moments of the ground and excited states of the three molecules and the transition dipole moments (TDMs) between the different states. Finally, using the calculated FCFs and TDMs, we determine that the A2Π1/2→X2Σ1/2 + transition is suitable for transverse cooling in BaF.

Material Size Dependence on Fundamental Constants.

Precise experimental setups for detection of variation of fundamental constants, scalar dark matter, or gravitational waves, such as laser interferometers, optical cavities, and resonant-mass detectors, are directly linked to measuring changes in material size. Here we present calculated and experiment-derived estimates for both α and µ dependence of lattice constants and bond lengths of selected solid-state materials and diatomic molecules that are needed for interpretation of such experiments.

Aggregation behavior of N-carboxyethylchitosan in aqueous solution: effects of pH, polymer concentration, and presence of a gemini surfactant.

A kind of biocompatible derivative of chitosan, N-carboxyethylchitosan (CECh) with a degree of substitution of 0.21 (DS 0.21) was synthesized by a Michael addition reaction. The aggregation behavior of CECh in aqueous solution under the effects of pH, polymer concentration, as well as a gemini surfactant, was investigated by turbidity, zeta potential, fluorescence spectroscopy, viscosity, and surface tension measurements. In the pH range of 3-11, the macroscopic phase separation of CECh from water occurs near the isoelectric point (IEP) due to the intense electrostatic attraction, and the intermolecular interaction at pH 4 is stronger than that at pH 10 over the whole CECh concentration region. The critical aggregation concentration (CAC) of CECh/12-n-12 (n=3, 6) in basic media is determined to be between 0.0010 and 0.0015 mmol/L, and the length of the surfactant spacer is found to play an important role in the interaction of 12-n-12 with CECh.