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Nature Nanotechnology · Dec 05, 2025

Bioengineered photosynthetic nanothylakoids reshape the inflammatory microenvironment for rheumatoid arthritis therapy

Reducing individual inflammatory factors does not always translate into clinical efficacy in rheumatoid arthritis (RA), an autoimmune disease characterized by joint inflammation. Proinflammatory M1 macrophages are a key driver of the hyperinflammatory joint microenvironment, which also promotes the progression of RA. Here we show that folate-receptor-targeted photosynthetic nanothylakoid (FA-PEG-NTK)-based phototherapy reprogrammes macrophages from M1 to anti-inflammatory M2, and successfully remodels the inflammatory RA microenvironment. The nanothylakoids were sourced from plant-derived thylakoids and developed by surface modification with distearoyl phosphoethanolamine–polyethylene glycol (PEG) via hydrophobic interactions to preserve their photocatalytic enzymes. We show that upon light irradiation in a mouse macrophage model of inflammation, the FA-PEG-NTK system generates oxygen and nicotinamide adenine dinucleotide phosphate, alleviating hypoxia and reducing reactive oxygen species. This rebalances the oxidative stress in M1 macrophages, thereby remodelling the inflammatory microenvironment in RA. We also show that in a collagen-induced arthritis rat model, FA-PEG-NTK-mediated phototherapy notably alleviated synovial hyperplasia and enhanced bone and cartilage regeneration, outperforming the clinical treatment methotrexate, with no apparent side effects.

Biomedical engineering Drug delivery Nanostructures Tissue engineering and regenerative medicine biology mouse experiments
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Nature Nanotechnology · Dec 04, 2025

Geometry-induced spin chirality in a non-chiral ferromagnet at zero field

Spin chirality is a fundamental property that manifests non-reciprocal transport—magnetochiral anisotropy (MChA). However, the application of MChA in technology is constrained by the necessity for an external magnetic field, complex non-centrosymmetric crystal synthesis and cryogenic environments. Here we overcome these challenges by imprinting geometric chirality onto a nickel tube via three-dimensional nanoengineering. We use two-photon lithography to create a structurally twisted polymeric template with micrometre-sized pitch and diameters and cover it with a uniform 30-nm-thick nickel shell. The nickel tube exhibits spontaneous MChA—non-reciprocal transport at zero magnetic field and room temperature. X-ray magnetic circular dichroism microscopy confirms helical spin textures stabilized by the torsion- and curvature-engineered shape anisotropy, while inelastic light scattering spectroscopy demonstrates robust non-reciprocal magnon transport at remanence, reconfigurable via magnetic field history. The chiral parameter in our device surpasses that of natural chiral magnets such as Cu2OSeO3. Analytical theory and micromagnetic simulations demonstrate that the non-reciprocity is further enhanced by downscaling the feature sizes. Our results establish a scalable, geometry-driven nanotechnology that imprints spin chirality on non-chiral ferromagnets and may enable nanoscale integration of chirality-enhanced magnonics and spintronics for real-world use cases.

Magnetic devices Magnetic properties and materials Spintronics other
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Nature Nanotechnology · Nov 17, 2025

Efficient CO2-to-methanol electrocatalysis in acidic media via microenvironment-tuned cobalt phthalocyanine

Electrosynthesis of value-added chemicals in strong acids can mitigate carbon loss and the operational cost of CO2reduction reaction (CO2RR). However, molecular catalysis for CO2RR is typically conducted in neutral or alkaline environments. CO2RR in acidic media is challenged by the scarcity of catalyst candidates, competitive hydrogen evolution and slow product formation. Here we report a locally ionic yet simultaneously hydrophobic and aerophilic layered structure that modulates the microenvironment surrounding cobalt phthalocyanine (CoPc) molecular catalysts, enabling efficient, multielectron CO2RR in acidic media. Experiment and theoretical modelling reveal that the polarized electrostatic field arising from the cationic groups suppresses hydronium migration. Concurrently, the van der Waals forces between the reactant gas and alkyl groups improve local CO availability, combining to achieve a methanol partial current density of 132 mA cm−2with 62% selectivity at a pH of ~1 and –1.37 VRHEfor CoPc, exceeding previous reports on neutral or alkaline electrolytes. The improved CO coverage also enables the detection of *CHO and *CO intermediates from in situ spectroscopy. We validate our strategy on various molecules, which champion the efficient inhibition of hydrogen evolution and improved CO2RR partial current density in acidic media. CoPc-based layered structure with similar ionic, hydrophobic and aerophilic interfaces also yields comparable methanol productivity.

Electrocatalysis Molecular dynamics Electrocatalysis CO2 Reduction Molecular Catalysis Acidic Media
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Nature Nanotechnology · Nov 17, 2025

Nanoengineered aqueous-hydrotrope hybrid liquid electrolyte solutions for efficient zinc batteries across a wide temperature range

Aqueous zinc metal batteries are ideal candidates for grid storage applications. However, their practical application is hindered by a narrow operating temperature range and a limited electrolyte electrochemical stability window, both of which can be attributed to the water activity. Here, to minimize water activity in the electrolyte solution, we introduce a nanoengineered approach in which the water molecules are confined within a hydrophilic–hydrophobic water solvation sheath. The hydrogen-bond interaction with the hydrophilic groups in the inner solvation layer effectively suppresses water decomposition, and the hydrophobic solvents in the outer solvation layer establish a repulsive effect against water molecules. As a proof of concept, a hydrophobic and non-polar hydrofluoroether cosolvent is introduced into a Zn-ion aqueous electrolyte solution and tested together with various fluorinated hydrotrope molecules to favour the compatibility of the cosolvent with water. By such a water confinement strategy, an average Zn plating/stripping reversibility of 99.92% is achieved for over 4,000 cycles at 2.0 mA cm−2and 2.0 mAh cm−2in a Zn||Cu coin cell configuration. When tested in a Zn||VOPO4·2H2O lab-scale cell configuration, the selected aqueous-hydrotrope hybrid electrolyte solution enables long-lasting and highly reversible battery performance across temperatures from −80 °C to +60 °C.

Analytical chemistry Batteries Electrochemistry Energy storage Materials for energy and catalysis Battery Technology Electrolyte Engineering Zinc Batteries Energy Storage
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Nature Nanotechnology · Nov 17, 2025

All-optical modulation with single photons using an electron avalanche

The distinctive characteristics of light, such as high-speed and low-loss propagation, low crosstalk and low power consumption, along with the unique quantum properties of photons, make it most suitable for various applications in communications, high-resolution imaging, optical computing and quantum information technologies. One limiting factor, however, is the weak optical nonlinearity of conventional media, which poses challenges for controlling light at ultralow intensities. Here we demonstrate all-optical modulation of the refractive index enabled by the electron avalanche process in silicon using a control beam with single-photon light intensities. The observed process corresponds to an extremely high nonlinear refractive index of\({n}_{2}\approx 1.3\times {10}^{-2}\,{{\rm{m}}}^{2}\,{{\rm{W}}}^{-1}\), which is several orders of magnitude higher than those of the best-known nonlinear optical materials. Using single photons for light modulation opens the possibility of gigahertz-frequency—and potentially even faster—optical switching for on-chip photonic and quantum devices operating at room temperature.

Nonlinear optics Photonic devices Quantum optics Silicon photonics
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Nature Nanotechnology · Nov 14, 2025

Nanoscale domains govern local diffusion and ageing within fused-in-sarcoma condensates

Biomolecular condensates regulate cellular physiology by sequestering and processing RNAs and proteins, yet how these processes are locally tuned within condensates remains unclear. Moreover, in neurodegenerative diseases such as amyotrophic lateral sclerosis, condensates undergo liquid-to-solid phase transitions, but capturing early intermediates in this process has been challenging. Here we present a surface multi-tethering approach to achieve intra-condensate single-molecule tracking of fluorescently labelled RNA and protein molecules within liquid-like condensates. Using RNA-binding protein fused-in-sarcoma as a model for condensates implicated in amyotrophic lateral sclerosis, we discover that RNA and protein diffusion is confined within distinct nanometre-scale domains, or nanodomains, which exhibit unique connectivity and chemical environments. The properties of these nanodomains are tunable by guest molecules. As condensates age, nanodomains reposition, facilitating fused-in-sarcoma fibrilization at the condensate surface, a process further enhanced by anti-amyotrophic lateral sclerosis drugs. Our findings demonstrate that nanodomain formation governs condensate function by modulating the residence time and spatial organization of constituent biomolecules, providing previously unattainable insights into condensate ageing and mechanisms underlying disease.

Molecular self-assembly Nanoparticles biology
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Nature Nanotechnology · Nov 11, 2025

Lumen charge governs gated ion transport in β-barrel nanopores

β-Barrel nanopores are involved in crucial biological processes, from ATP export in mitochondria to bacterial resistance, and represent a promising platform for emerging sequencing technologies. However, in contrast to ion channels, the understanding of the fundamental principles governing ion transport through these nanopores remains largely unexplored. Here we integrate experimental, numerical and theoretical approaches to elucidate ion transport mechanisms in β-barrel nanopores. We identify and characterize two distinct nonlinear phenomena: open-pore rectification and gating. Through extensive mutation analysis of aerolysin nanopores, we demonstrate that open-pore rectification is caused by ionic accumulation driven by the distribution of lumen charges. In addition, we provide converging evidence suggesting that gating is controlled by electric fields dissociating counterions from lumen charges, promoting local structural deformations. Our findings establish a rigorous framework for characterizing and understanding ion transport processes in protein-based nanopores, enabling the design of adaptable nanofluidic biotechnologies. We illustrate this by optimizing an aerolysin mutant for computing applications.

Bionanoelectronics Electrical and electronic engineering Nanopores biology
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Nature Nanotechnology · Nov 07, 2025

Degradable cyclic amino alcohol ionizable lipids as vectors for potent influenza mRNA vaccines

The next generation of mRNA vaccines must address several limitations, including enhancing vaccine potency and reducing toxicity. Here we develop a class of degradable, cyclic amino ionizable lipids via sequential combinatorial chemistry and rational design. Lipid nanoparticles (LNPs) formulated with the top-performing ionizable lipid, AMG1541, elicited similar protective neutralization antibody titres against an H3 influenza antigen when compared with the FDA-approved ionizable lipid SM-102 at a 100-fold lower dose, with enhanced clearance in vivo. AMG1541 mRNA LNPs substantially reduced expression in the liver following intramuscular injection, mitigating the associated toxicity. We also observed improved mRNA delivery to antigen-presenting cells at the injection site and the draining lymph node, leading to stronger germinal centre reactions. Structure–activity relationship studies suggest that cyclic headgroups and β-amino alcohols facilitate interactions with the mRNA backbone and enhance endosomal escape. The formulations developed here significantly enhance the potency of mRNA vaccines, and our structural insights may guide the development of next-generation vaccine delivery systems.

Chemical engineering Nanoparticles biology