Nature nanotechnology最新文献

In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR–Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is challenging. Here we demonstrate a polymer-locking fusogenic liposome (Plofsome) that can be transported across the blood–brain barrier (BBB) and deliver short interfering RNA or CRISPR–Cas9 ribonucleoprotein complexes into the cytoplasm of GBM cells. Plofsome is designed by integrating a ‘lock’ into the fusogenic liposome using a traceless reactive oxygen species (ROS)-cleavable linker so that fusion occurs only after crossing the BBB and entering the GBM tissue with high ROS levels. Our results showed that MDK suppression by Plofsomes significantly reduced TMZ resistance and inhibited GBM growth in orthotopic brain tumour models. Importantly, Plofsomes are effective only at tumour sites and not in normal tissues, which improves the safety of combined RNAi and CRISPR–Cas9 therapeutics.

Infectious diseases and cancer evade immune surveillance using similar mechanisms. Targeting immune mechanisms using common strategies thus represents a promising avenue to improve prevention and treatment. Synthetic immunology can provide such strategies by applying engineering principles from synthetic biology to immunology. Synthetic biologists engineer cells by top-down genetic manipulation or bottom-up assembly from nanoscale building blocks. Recent successes in treating advanced tumours and diseases using genetically engineered immune cells highlight the power of the top-down synthetic immunology approach. However, genetic immune engineering is mostly limited to ex vivo applications and is subject to complex counter-regulation inherent to immune functions. Bottom-up synthetic biology can harness the rich nanotechnology toolbox to engineer molecular and cellular systems from scratch and equip them with desired functions. These are beginning to be tailored to perform targeted immune functions and should hence allow intervention strategies by rational design. In this Perspective we conceptualize bottom-up synthetic immunology as a new frontier field that uses nanotechnology for crucial innovations in therapy and the prevention of infectious diseases and cancer.

An immunosuppressive tumour microenvironment strongly influences response rates in patients receiving immune checkpoint blockade-based cancer immunotherapies, such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1). Here we demonstrate that metal-ion-chelating L-phenylalanine nanostructures synergize with short-term starvation (STS) to remodel the immunosuppressive microenvironment of breast and colorectal tumours. These nanostructures modulate the electrophysiological behaviour of dendritic cells and activate them through the NLRP3 inflammasome and calcium-mediated nuclear factor-κB pathway. STS promotes the cellular uptake of nanostructures through amino acid transporters and plays a key role in dendritic cell maturation and tumour-specific cytotoxic T lymphocyte responses. This study demonstrates the potential role of metal-ion-chelating L-phenylalanine nanostructures in activating immune responses and the effect of STS treatment in improving nanomaterial-mediated cancer immunotherapy.

To control and enhance light-matter interactions at the nanoscale, two parameters are central: the spectral overlap between an optical cavity mode and the material's spectral features (for example, excitonic or molecular absorption lines), and the quality factor of the cavity. Controlling both parameters simultaneously would enable the investigation of systems with complex spectral features, such as multicomponent molecular mixtures or heterogeneous solid-state materials. So far, it has been possible only to sample a limited set of data points within this two-dimensional parameter space. Here we introduce a nanophotonic approach that can simultaneously and continuously encode the spectral and quality-factor parameter space within a compact spatial area. We use a dual-gradient metasurface design composed of a two-dimensional array of smoothly varying subwavelength nanoresonators, each supporting a unique mode based on symmetry-protected bound states in the continuum. This results in 27,500 distinct modes and a mode density approaching the theoretical upper limit for metasurfaces. By applying our platform to surface-enhanced molecular spectroscopy, we find that the optimal quality factor for maximum sensitivity depends on the amount of analyte, enabling effective molecular detection regardless of analyte concentration within a single dual-gradient metasurface. Our design provides a method to analyse the complete spectral and coupling-strength parameter space of complex material systems for applications such as photocatalysis, chemical sensing and entangled photon generation.

Due to quasi-one-dimensional confinement, nanowires possess unique electronic properties, which can promote specific device architectures. However, nanowire growth presents paramount challenges, limiting the accessible crystal structures and elemental compositions. Here we demonstrate solid-state topotactic exchange that converts wurtzite InAs nanowires into Zintl Eu₃In₂As₄. Molecular-beam-epitaxy-based in situ evaporation of Eu and As onto InAs nanowires results in the mutual exchange of Eu from the shell and In from the core. Therefore, a single-phase Eu₃In₂As₄ shell grows, which gradually consumes the InAs core. The mutual exchange is supported by the substructure of the As matrix, which is similar across the wurtzite InAs and Zintl Eu₃In₂As₄ and therefore is topotactic. The Eu₃In₂As₄ nanowires undergo an antiferromagnetic transition at a Néel temperature of ~6.5 K. Ab initio calculations confirm the antiferromagnetic ground state and classify Eu₃In₂As₄ as a C₂T axion insulator, hosting both chiral hinge modes and unpinned Dirac surface states. The topotactic mutual-exchange nanowire growth will, thus, enable the exploration of intricate magneto-topological states in Eu₃In₂As₄ and potentially in other exotic compounds.

Biomolecule-based non-covalent glasses are biocompatible and biodegradable, and offer a sustainable alternative to conventional glass. Cyclic peptides (CPs) can serve as promising glass formers owing to their structural rigidity and resistance to enzymatic degradation. However, their potent crystallization tendency hinders their potential in glass construction. Here we engineered a series of CP glasses with tunable glass transition behaviours by modulating the conformational complexity of CP clusters. By incorporating multicomponent CPs, the formation of high-entropy CP glass is facilitated, which-in turn-inhibits the crystallization of individual CPs. The high-entropy CP glass demonstrates enhanced mechanical properties and enzyme tolerance compared with individual CP glass and a unique biorecycling capability that is unattainable by traditional glasses. These findings provide a promising paradigm for the design and development of stable non-covalent glasses based on naturally derived biomolecules, and advance their application in pharmaceutical formulations and smart functional materials.

Lipid nanoparticle (LNP)–mRNA complexes are transforming medicine. However, the medical applications of LNPs are limited by their low endosomal disruption rates, high toxicity and long tissue persistence times. LNPs that rapidly hydrolyse in endosomes (RD-LNPs) could solve the problems limiting LNP-based therapeutics and dramatically expand their applications but have been challenging to synthesize. Here we present an acid-degradable linker termed ‘azido-acetal’ that hydrolyses in endosomes within minutes and enables the production of RD-LNPs. Acid-degradable lipids composed of polyethylene glycol lipids, anionic lipids and cationic lipids were synthesized with the azido-acetal linker and used to generate RD-LNPs, which significantly improved the performance of LNP–mRNA complexes in vitro and in vivo. Collectively, RD-LNPs delivered mRNA more efficiently to the liver, lung, spleen and brains of mice and to haematopoietic stem and progenitor cells in vitro than conventional LNPs. These experiments demonstrate that engineering LNP hydrolysis rates in vivo has great potential for expanding the medical applications of LNPs.

Thermal emission from a hot body is inherently challenging to control due to its incoherent nature. Recent advances have shown that patterned surfaces can transform thermal emission into partially coherent beams with tailored directionality and frequency selectivity. Here we experimentally demonstrate polarization-selective, unidirectional and narrowband thermal emission using single-layer metasurfaces. By implementing polarization gradients across the surface, we unveil a generalization of the photonic Rashba effect from circular polarizations to any pair of orthogonal polarizations and apply it to thermal emission. Leveraging pointwise specification of arbitrary elliptical polarization, we implement a thermal geometric phase and leverage it to prove previous theoretical predictions that asymmetric chiral emission is possible without violating reciprocity. This general platform can be extended to other frequency regimes in efforts to compactify metasurface optics technologies without the need for external coherent sources.

Any modern information system is expected to feature a set of primordial features and functions: a substrate stably carrying data; the ability to repeatedly write, read, erase, reload and compute on specific data from that substrate; and the overall ability to execute such functions in a seamless and programmable manner. For nascent molecular information technologies, proof-of-principle realization of this set of primordial capabilities would advance the vision for their continued development. Here we present a DNA-based store and compute engine that captures these primordial capabilities. This system comprises multiple image files encoded into DNA and adsorbed onto ~50-μm-diameter, highly porous, hierarchically branched, colloidal substrate particles comprised of naturally abundant cellulose acetate. Their surface areas are over 200 cm² mg⁻¹ with binding capacities of over 10¹² DNA oligos mg⁻¹, 10 TB mg⁻¹ or 10⁴ TB cm⁻³. This ‘dendricolloid’ stably holds DNA files better than bare DNA with an extrapolated ability to be repeatedly lyophilized and rehydrated over 170 times compared with 60 times, respectively. Accelerated ageing studies project half-lives of ~6,000 and 2 million years at 4 °C and −18 °C, respectively. The data can also be erased and replaced, and non-destructive file access is achieved through transcribing from distinct synthetic promoters. The resultant RNA molecules can be directly read via nanopore sequencing and can also be enzymatically computed to solve simplified 3 × 3 chess and sudoku problems. Our study establishes a feasible route for utilizing the high information density and parallel computational advantages of nucleic acids.