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Current antisense oligonucleotide (ASO) therapies for the treatment of central nervous system (CNS) disorders are performed through invasive administration, thereby placing a major burden on patients. To alleviate this burden, we herein report systemic ASO delivery to the brain by crossing the blood–brain barrier using glycemic control as an external trigger. Glucose‐coated polymeric nanocarriers, which can be bound by glucose transporter‐1 expressed on the brain capillary endothelial cells, are designed for stable encapsulation of ASOs, with a particle size of about 45 nm and an adequate glucose‐ligand density. The optimized nanocarrier efficiently accumulates in the brain tissue 1 h after intravenous administration and exhibits significant knockdown of a target long non‐coding RNA in various brain regions, including the cerebral cortex and hippocampus. These results demonstrate that the glucose‐modified polymeric nanocarriers enable noninvasive ASO administration to the brain for the treatment of CNS disorders., The sweet spot: Antisense‐oligonucleotide‐loaded glucosylated‐polyion‐complex micelles can be used for RNA knockdown in various brain regions using blood‐glucose level as an external trigger. Glucose transporter‐1 expressed on the brain capillary endothelial cells binds the glucose‐coated nanocarrier and transports it, along with its cargo, across the blood–brain barrier. This could be used for the treatment of disorders of the central nervous system.

Development of efficient delivery vehicles for in vitro transcribed mRNA (IVT mRNA) is currently a major challenge in nanomedicines. For systemic mRNA delivery, we developed a series of cationic amphiphilic polyaspartamide derivatives (PAsp(DET/R)s) carrying various alicyclic (R) moieties with diethylenetriamine (DET) in the side chains to form mRNA-loaded polyplexes bearing stability under physiological conditions and possessing endosomal escape functionality. While the size and ζ-potential of polyplexes were comparable among various PAsp(DET/R)s, the transfection efficiencies of polyplexes were considerably varied due to difference in the R moieties of PAsp(DET/R)s and were described by an octanol-water (or buffer at pH 7.3) distribution coefficient (logD

A family of compounds built by a single molecular species, $M$(${\mathrm{tmdt})}_{2}$, with a metal ion, $M$, and organic ligands, tmdt, affords diverse electronic phases due to $M$-dependent interplays between $d$ electrons in $M$, and $\ensuremath{\pi}$ electrons in tmdt. We investigated the spin state in $\mathrm{Pd}{(\mathrm{tmdt})}_{2}$, a $\ensuremath{\pi}$-electron system without a $d$-electron contribution, through $^{1}\mathrm{H}$ nuclear magnetic resonance (NMR) and muon-spin resonance experiments. The temperature profiles of the NMR linewidth, relaxation rate, and asymmetry parameter in muon decay show an inhomogeneous antiferromagnetic order with moments distributed around $\ensuremath{\sim}0.1{\ensuremath{\mu}}_{\mathrm{B}}$ that onsets at above 100 K. This result provides an example of the antiferromagnetic order in a pure $\ensuremath{\pi}$-electron system in $M$(${\mathrm{tmdt})}_{2}$, and it demonstrates that correlation among the $\ensuremath{\pi}$ electrons is so strong as to give the N\'eel temperature over 100 K. The small and inhomogeneous moments are understandable as the crucial disorder effect in correlated electrons situated near the Mott transition.

A new single-component palladium complex, [Pd(hfdt)2] (hfdt: bis(trifluoromethyl)tetrathiafulvalenedithiolate), was prepared. Single-crystal structure analysis showed that [Pd(hfdt)2] is a rare cas...

Stabilisation of fragile oligonucleotides, typically small interfering RNA (siRNA), is one of the most critical issues for oligonucleotide therapeutics. Many previous studies encapsulated oligonucleotides into ~100-nm nanoparticles. However, such nanoparticles inevitably accumulate in liver and spleen. Further, some intractable cancers, e.g., tumours in pancreas and brain, have inherent barrier characteristics preventing the penetration of such nanoparticles into tumour microenvironments. Herein, we report an alternative approach to cancer-targeted oligonucleotide delivery using a Y-shaped block catiomer (YBC) with precisely regulated chain length. Notably, the number of positive charges in YBC is adjusted to match that of negative charges in each oligonucleotide strand (i.e., 20). The YBC rendezvouses with a single oligonucleotide in the bloodstream to generate a dynamic ion-pair, termed unit polyion complex (uPIC). Owing to both significant longevity in the bloodstream and appreciably small size (~18 nm), the uPIC efficiently delivers oligonucleotides into pancreatic tumour and brain tumour models, exerting significant antitumour activity., Nanoparticle delivery of siRNA has problems with penetration and off target accumulation. Here, the authors report on the development of Y-shaped block catiomers which dynamically wrap around siRNA; demonstrate increased circulation times and delivery into hard to reach brain and pancreas tumour models.

Crystals of [Pd(tmdt)2] (tmdt = trimethylenetetrathiafulvalenedithiolate) were prepared in order to investigate their physical properties. The electrical resistivity of [Pd(tmdt)2] was measured on single crystals using two-probe methods and showed that the room-temperature conductivity was 100 S·cm(-1). The resistivity behaviors implied that [Pd(tmdt)2] was a semimetal at approximately room temperature and became narrow-gap semiconducting as the temperature was decreased to the lowest temperature. X-ray structural studies on small single crystals of [Pd(tmdt)2] at temperatures of 20-300 K performed using synchrotron radiation at SPring-8 showed no distinct structural change over this temperature region. However, small anomalies were observed at approximately 100 K. Electron spin resonance (ESR) spectra were measured over the temperature range of 2.7-301 K. The ESR intensity increased as the temperature decreased to 100 K and then decreased linearly as the temperature was further decreased to 50 K, where an abrupt decrease in the intensity was observed. To investigate the magnetic state, (1)H nuclear magnetic resonance (NMR) measurements were performed in the temperature range of 2.5-271 K, revealing broadening below 100 K. The NMR relaxation rate gradually increased below 100 K and formed a broad peak at approximately 50 K, followed by a gradual decrease down to the lowest temperature. These results suggest that most of the sample undergoes the antiferromagnetic transition at approximately 50 K with the magnetic ordering temperatures distributed over a wide range up to 100 K. These electric and magnetic properties of [Pd(tmdt)2] are quite different from those of the single-component molecular (semi)metals [Ni(tmdt)2] and [Pt(tmdt)2], which retain their stable metallic states down to extremely low temperatures. The experimental results and the band structure calculations at the density functional theory level showed that [Pd(tmdt)2] may be an antiferromagnetic Mott insulator with a strong electron correlation.

Molecular metal complexes with interactions between localized spins and conduction electrons are expected to show interesting electronic and magnetic properties. We prepared magnetic molecular cond...