Coherent acoustic vibrations of Au nanoblocks and their modulation by Al2O3 layer deposition.

Coherent acoustic phonons induced in metallic nanostructures have attracted tremendous attention owing to their unique optomechanical characteristics. The frequency of the acoustic phonon vibration is highly sensitive to the material adsorption on metallic nanostructures and, therefore, the acoustic phonon offers a promising platform for ultrasensitive mass sensors. However, the physical origin of acoustic frequency modulation by material adsorption has been partially unexplored so far. In this study, we prepared Al2O3-deposited Au nanoblocks and measured their acoustic phonon frequencies using time-resolved pump-probe measurements. By precisely controlling the thickness of the Al2O3 layer, we systematically investigated the relation between the acoustic phonon frequency and the deposited Al2O3 amounts. The time-resolved measurements revealed that the acoustic breathing modes were predominantly excited in the Au nanoblocks, and their frequencies increased with the increment of the Al2O3 thickness. From the relationship between the acoustic phonon frequency and the Al2O3 thickness, we revealed that the acoustic phonon frequency modulation is attributed to the density change of the whole sample. Our results would provide fruitful information for developing quantitative mass sensing devices based on metallic nanostructures.

Preparation of photonic molecular trains via soft-crystal polymerization of lanthanide complexes.

Soft-crystals are defined as flexible molecular solids with highly ordered structures and have attracted attention in molecular sensing materials based on external triggers and environments. Here, we show the soft-crystal copolymerization of green-luminescent Tb(III) and yellow-luminescent Dy(III) coordination centers. Soft-crystal polymerization is achieved via transformation of monomeric dinuclear complexes and polymeric structures with respect to coordination number and geometry. The structural transformation is characterized using single-crystal and powder X-ray diffraction. The connected Tb(III) crystal-Dy(III) crystal show photon energy transfer from the Dy(III) centre to the Tb(III) centre under blue light excitation (selective Dy(III) centre excitation: 460 ± 10 nm). The activation energy of the energy transfer is estimated using the temperature-dependent emission lifetimes and emission quantum yields, and time-dependent density functional theory (B3LYP) calculations. Luminescence-conductive polymers, photonic molecular trains, are successfully prepared via soft-crystal polymerization on crystal media with remarkable long-range energy migration.

The Effects of Chimeric Antigen Receptor (CAR) Hinge Domain Post-Translational Modifications on CAR-T Cell Activity.

To improve the efficacy and safety of chimeric antigen receptor (CAR)-expressing T cell therapeutics through enhanced CAR design, we analysed CAR structural factors that affect CAR-T cell function. We studied the effects of disulphide bonding at cysteine residues and glycosylation in the HD on CAR-T function. We used first-generation CAR[V/28/28/3z] and CAR[V/8a/8a/3z], consisting of a mouse vascular endothelial growth factor receptor 2 (VEGFR2)-specific single-chain variable fragment tandemly linked to CD28- or CD8α-derived HD, transmembrane domain (TMD) and a CD3ζ-derived signal transduction domain (STD). We constructed structural variants by substituting cysteine with alanine and asparagine (putative N-linked glycosylation sites) with aspartate. CAR[V/28/28/3z] and CAR[V/8a/8a/3z] formed homodimers, the former through a single HD cysteine residue and the latter through the more TMD-proximal of the two cysteine residues. The absence of disulphide bonds did not affect membrane CAR expression but reduced antigen-specific cytokine production and cytotoxic activity. CAR[V/28/28/3z] and CAR[V/8a/8a/3z] harboured one N-linked glycosylation site, and CAR[V/8a/8a/3z] underwent considerable O-linked glycosylation at an unknown site. Thus, N-linked glycosylation of CAR[V/28/28/3z] promotes stable membrane CAR expression, while having no effect on the expression or CAR-T cell activity of CAR[V/8a/8a/3z]. Our findings demonstrate that post-translational modifications of the CAR HD influence CAR-T cell activity, establishing a basis for future CAR design.

Observation of the plasmon mode transition from triangular to hexagonal nanoplates.

The geometrical shape of a metal nanostructure plays an essential role in determining the optical functionality of plasmonic cavity modes. Here, we investigate the geometrical modification effect on plasmonic cavity modes induced in two-dimensional gold nanoplates. We perform near-field transmission measurements on triangular and tip-truncated triangular nanoplates and reveal that the plasmonic cavity modes are qualitatively consistent with each other as long as the snipping size is not significant. To elucidate the tip-truncation effect on plasmonic cavity modes in detail, we carry out numerical simulations for nanoplates with various snipping sizes and find that tip truncation affects not only the optical selection rules but also the energy relation for the plasmonic cavity modes. These findings provide a foundation for the rational design of plasmonic cavities with desired optical functionality.

Photoinduced Copper-Catalyzed Asymmetric Acylation of Allylic Phosphates with Acylsilanes.

We report a visible-light-induced copper-catalyzed highly enantioselective umpolung allylic acylation reaction with acylsilanes as acyl anion equivalents. Triplet-quenching experiments and DFT calculations supported our reaction design, which is based on copper-to-acyl metal-to-ligand charge transfer (MLCT) photoexcitation that generates a charge-separated triplet state as a highly reactive intermediate. According to the calculations, the allylic phosphate substrate in the excited state undergoes novel molecular activation into an allylic radical weakly bound to the copper complex. The allyl radical fragment undergoes copper-mediated regio- and stereocontrolled coupling with the acyl group under the influence of the chiral N-heterocyclic carbene ligand.

Predicting the Efficacy and Safety of TACTICs (Tumor Angiogenesis-Specific CAR-T Cells Impacting Cancers) Therapy for Soft Tissue Sarcoma Patients.

Soft tissue sarcomas (STSs) are heterogeneous and aggressive malignancies with few effective therapies available. We have developed T cells expressing a vascular endothelial growth factor receptor 2 (VEGFR2)-specific chimeric antigen receptor (CAR) to establish a tumor angiogenesis-specific CAR-T cells impacting cancers (TACTICs) therapy. In this study, we optimized the manufacturing and transportation of mRNA-transfected anti-VEGFR2 CAR-T cells and collected information that allowed the extrapolation of the efficacy and safety potential of TACTICs therapy for STS patients. Although 5-methoxyuridines versus uridines did not improve CAR-mRNA stability in T cells, the utilization of CleanCap as a 5' cap-structure extended the CAR expression level, increasing VEGFR2-specific cytotoxicity. Furthermore, 4 °C preservation conditions did not affect the viability/cytotoxicity of CAR-T cells, contrarily to a freeze-thaw approach. Importantly, immunohistochemistry showed that most of the STS patients' specimens expressed VEGFR2, suggesting a great potential of our TACTICs approach. However, VEGFR2 expression was also detected in normal tissues, stressing the importance of the application of a strict monitoring schedule to detect (and respond to) the occurrence of adverse effects in clinics. Overall, our results support the development of a "first in humans" study to evaluate the potential of our TACTICs therapy as a new treatment option for STSs.

Spatial characteristics of optical fields near a gold nanorod revealed by three-dimensional scanning near-field optical microscopy.

We visualize plasmon mode patterns induced in a single gold nanorod by three-dimensional scanning near-field optical microscopy. From the near-field transmission imaging, we find that 3rd and 4th order plasmon modes are resonantly excited in the nanorod. We perform electromagnetic simulations based on the discrete dipole approximation method under focused Gaussian beam illumination and demonstrate that the observed near-field spectral and spatial features are well reproduced by the simulation. We also reveal from the three-dimensional near-field microscopy that the 4th order plasmon mode confines optical fields more tightly compared with the 3rd order mode. This result indicates that the even-order plasmon modes are promising for enhancing the light-matter interactions.

Characterization of Overlapped Plasmon Modes in a Gold Hexagonal Plate Revealed by Three-Dimensional Near-Field Optical Microscopy.

A detailed characterization of plasmon modes is important not only for a deeper understanding of plasmons but also for their practical applications. In this study, we investigated the three-dimensional near-field characteristics of high-order plasmon modes excited in a gold hexagonal nanoplate. From the near-field spectroscopic images, we found that both in-plane and out-of-plane plasmon modes observed near 900 nm were spectrally and spatially overlapped. We performed three-dimensional near-field measurement to reveal the optical characteristics of the overlapped modes in detail. We found that the steric near-field distribution near the nanoplate strongly depended on the plasmon mode, and the out-of-plane mode confines electromagnetic fields more tightly than the in-plane mode. We also found that the in-plane mode was dominantly visualized as the probe tip-sample distance increased. These findings demonstrate that the three-dimensional near-field technique enables selective visualization of a single plasmon mode even if multiple modes are spatially and spectrally overlapped.

Static and Dynamic Near-Field Measurements of High-Order Plasmon Modes Induced in a Gold Triangular Nanoplate.

Precise understanding of the spatiotemporal characteristics of plasmons is essential for the development of applications of plasmonic nanoparticles. In this study, we investigated the spatiotemporal properties of high-order plasmon modes induced in a gold triangular nanoplate by static and dynamic near-field measurements. The near-field transmission measurements revealed that in-plane and out-of-plane polarized plasmon modes were simultaneously excited and these modes spectroscopically and spatially overlapped. The superposition of these modes was visualized in the near-field two-photon excitation image of the nanoplate. We performed time-resolved autocorrelation measurements on the nanoplate and found that the correlation width was broader than the excitation pulse due to the plasmon dephasing process. From the correlation width map of the nanoplate, we experimentally demonstrated that the out-of-plane plasmon mode exhibits a longer dephasing time than the in-plane plasmon mode. These findings indicate that the out-of-plane mode is desirable for improving the performance of plasmons in various applications.

Optical control of plasmonic fields by phase-modulated pulse excitations.

We developed an advanced near-field optical method by combining an ultrafast near-field optical microscope with a prism-based pulse shaping system. We used this apparatus to visualize plasmonic optical fields and to measure the lifetime of plasmons excited on a rough gold film. We also studied the influence of the phase-modulation of the excitation pulse on the spatial distribution of the optical fields. We found that the spatial distribution of the optical fields can be controlled by a negatively chirped pulse.