Antiadhesive Nanosomes Facilitate Targeting of the Lysosomal GlcNAc Salvage Pathway through Derailed Cancer Endocytosis

Activated endocytosis of extracellular macromolecules and their intracellular trafficking to lysosomes is an essential metabolic mechanism in cancer cells during their rapid proliferation. Cancer cells reuse a vast amount of N‐acetylglucosamine (GlcNAc) supplied from the GlcNAc salvage pathway for the accelerated synthesis of a pivotal uridine diphosphate (UDP)‐GlcNAc. A method to inactivate key glycosidases in lysosomes could critically contribute to the development of potent anticancer therapy. Here we demonstrate that “nanosomes” made of core metals covered by an antiadhesive mixed self‐assembled monolayer allow for avoiding nonspecific surface protein corona and targeted molecular delivery through activated endocytosis. Nanosomes carrying suicide substrates showed that lysosomal glycosidases such as β‐hexosaminidase and β‐galactosidase in cancer cells are promising targets for novel anticancer therapeutic nanomedicine that induce apoptotic cell death through lysosomal membrane permeabilization. The advantage of this method is evident because multivalent surface loading by antiadhesive nanosomes makes it possible to highlight “weak interactions” such as carbohydrate–lectin interactions independent of surface protein corona.     

Far‐ and Deep‐Ultraviolet Surface Plasmon Resonance Sensor

Plasmonics in the UV region has been widely focused because of the higher energy and the abundant electronic resonances compared to the conventional visible plasmonics. Recently, we have investigated the surface plasmon resonance (SPR) properties of the Al film, aiming for the application as refractive index sensors. Utilizing the UV lights, we expect three advantages: high sensitivity, material selectivity, and surface selectivity. By using an original attenuated total reflectance spectroscopic instrument, Al‐SPR angle and wavelength were investigated with changing environments on the Al film. Al film thickness and materials of prisms on which Al was evaporated were also important factors for the SPR properties. By optimizing the conditions, the Al film worked as a sensor both in air and in liquids. In addition, our established system expands the plasmonics into an even higher energy region than 200 nm, while the UV‐plasmonics have been studied in the wavelength region longer than 200 nm.     

Source/drain engineering for MOSFETs with embedded-Si:C technology

Embedded silicon carbon alloy (e-Si:C) technology for source and drain (S/D) is expected to improve nMOSFET drive current. The distribution and activation characteristics of arsenic in Si:C film and the interfacial solid-phase reaction of the Ni/Si:C system were studied with the aim of achieving the maximum improvement of the characteristics of e-Si:C S/D. It was clarified that the active carrier concentration of Si:C decreased with increasing carbon concentration compared to the control Si. There is concern that the low doping activation in Si:C increases series resistance of e-Si:C S/D nMOSFETs and degrades the performance gain expected from the strain effect.     

Peripheral Modifications of meso-Hydroxyporphyrins: Formation of π-Electronic Anions and Ion-Pairing Assemblies

Phenyl groups were introduced at the β-positions proximal to the meso-hydroxy moiety in hydroxyporphyrin Ni^II complexes by oxidized BINAP Pd^II complexes. Ion-pairing assemblies of deprotonated π-electronic anions, anionic site of which was stabilized by the introduced phenyl moieties with a bulky cation, were formed. They showed charge-by-charge assemblies, assembly modes of which were modulated by the anionic building units.     

Dissolution kinetics of K-alum crystals as judged from the measurements of surface undersaturations

The normal dissolution rates, the slopes and the average velocities of dissolution steps of etch pits on the (111) face of a K-alum crystal, originating from dislocations with Burgers vector 110, were measured in relation to the surface undersaturations. From the mutual relations, it was shown that the dissolution was controlled by both diffusion and surface kinetic processes, although the contribution of the latter process was smaller than in the case of growth. It was also demonstrated that the normal dissolution rate was always larger than the growth rate. This is attributed to the fact that the slopes of growth hillocks are invariably smaller than those of etch pits.     

Second-generation total synthesis of haterumalide NA using B-alkyl Suzuki-Miyaura coupling

Second-generation total synthesis of haterumalide NA, a potent cytotoxic marine macrolide, was achieved by using B-alkyl Suzuki-Miyaura coupling and Nozaki-Hiyama-Kishi coupling as key steps (1.2% in 33 steps). Compared to our first-generation approach, the second-generation synthesis is much improved in the yield of key intermediate.     

Substitution, dimerization, metalation, and ring-opening reactions of N-fused porphyrins

A variety of reactions such as substitution, dimerization, rhenium(I) metalation, and ring-opening reactions of N-fused porphyrin (NFP) and optical properties of the products are presented. Palladium-catalyzed cross-coupling reactions under Suzuki or Stille conditions afford aryl and arylethynyl-substituted NFPs (12, 14) and an ethynyl-bridged dimer (15) from 3-bromo-substituted NFP (3b) in 40-98% yields. Treatment of NFP with silver(I) trifluoroacetate in CHCl₃ affords a dimer (22) linked at both C21-positions of the fused rings and its bis-Re(I) metal complex (24) is synthesized. X-ray structures of the 3-trifluoromethyl and 3-phenyl NFP derivatives (9e and 12a) reveal the three-center hydrogen bondings in the core. All the new NFP derivatives display unique absorption spectra, and particularly, ethyne-bridged NFP-dimer (15) shows a remarkable bathochromic shift into a near-infrared region showing an absorption band at 1020 nm with tailing up to 1100 nm. Moreover, alkoxide nucleophiles convert NFP into NCP derivatives by the cleavage of C-N bond in the fused ring, which is useful for the preparation of various C3-substituted NCPs and C21,C21′-linked NCP dimers from NFPs.