Nature nanotechnology最新文献

Intra-articular RNA therapeutics have shown promise in osteoarthritis (OA); however, maximizing their efficacy requires targeted delivery to degenerating cartilage within focal lesions. As OA progresses, cartilage degeneration worsens, necessitating disease-responsive targeting with enhanced delivery in advanced stages. Here we develop an anionic nanoparticle (NP) strategy for targeting glycosaminoglycan loss, a hallmark of OA's progression that reduces cartilage's negative charge. These NPs selectively diffuse and accumulate into matrix regions inversely correlated with glycosaminoglycan content owing to reduced electrostatic repulsion, a strategy we term 'matrix inverse targeting' (MINT). In a mouse model of OA, intra-articular delivery of luciferase messenger RNA-loaded MINT NPs demonstrated disease-severity-responsive expression. Using this strategy, we delivered ghrelin mRNA, as ghrelin has shown chondroprotection properties previously. Ghrelin mRNA-loaded MINT NPs reduced cartilage degeneration, subchondral bone thickening and nociceptive pain. Our findings highlight the potential of ghrelin mRNA delivery as a disease-modifying therapy for OA and the platform's potential for lesion-targeted RNA delivery responsive to disease severity.

Excitons are prevalent in many bosonic quantum phenomena in semiconductors. During their optical transitions, excitons not only emit or absorb photons, but also determine light propagation behaviours within the host medium. While absorption and emission processes have found numerous practical applications, chiefly in light-emitting diodes and solar cells, excitons' capability of manipulating light propagation remains largely underexplored. Here we observe negative refraction-light bending in the opposite direction to conventional refraction-in an excitonic van der Waals magnet, namely chromium sulphide bromide (CrSBr). We also develop an excitonic hyperlens on an integrated nanophotonic chip, whose functionality is mediated by the magnetic orders of CrSBr. Specifically, the observed negative refraction and hyperlens effects emerge when CrSBr is magnetically ordered, driven by a magnetic enhancement of excitonic resonances. This work establishes excitons in van der Waals magnets as a versatile platform for controlling anomalous light propagation at the nanoscale.

Control of charge and heat transport is essential for computing and thermal management technologies. Recent work with superconducting materials has shown rectified electrical supercurrents near liquid helium temperatures. However, despite large theoretical interest and expected impact on quantum technologies, no experiments have demonstrated control of nanoscale radiative heat currents at cryogenic temperatures. Here we study photon-mediated thermal transport in nanogaps between niobium and gold. Using novel scanning calorimetric probes and nanofabricated devices, we reveal a ~20-fold suppression of radiative heat transport, when niobium transitions from the metallic to the superconducting state. Taking advantage of this effect, we also demonstrate a niobium-based cryogenic thermal diode with a heat rectification ratio of 70%. The experimental techniques and advances presented here will enable studying nanoscale thermal transport in quantum materials and advancing thermal management of superconducting devices.

Surgical resection remains the primary treatment for most solid tumours, yet metastatic tumour cells remaining after surgery substantially contribute to cancer-related mortality and recurrence. Here we identify syntaxin 11 as a key regulator that enhances the expression of MHC I and co-stimulatory molecules CD80/CD86 on tumour cell membranes, enabling cancer cells to acquire dendritic-cell-like features. By overexpressing syntaxin 11 in autologous tumour cells obtained from surgical resections, we generated MHC I^high/CD80^high/CD86^high dendritic-cell-like cells. Utilizing the cell membranes of these modified cells, we engineered artificial dendritic-cell-like cell-derived vesicles as a personalized autologous nanovaccine for the immunotherapy of postoperative metastatic cancer. This nanovaccine substantially improves antigen delivery to lymphoid organs and enhances antigen presentation efficiency through tumour self-presentation, thereby disrupting traditional vaccine development paradigms. Our work provides a promising avenue for developing effective metastatic cancer immunotherapies and offers hope for personalized postoperative immunotherapy.

The development of micro- and nanorobots has amplified the demand for intelligent multifunctional machines in biomedical applications, but most microrobotic systems struggle to achieve the attributes needed for those applications. Here we introduce enzymatic microbubble robots that exhibit steerable motion, enhanced biodegradability, high in vivo imaging contrast, and effective targeting and penetration of disease sites. These microrobots feature natural protein shells modified with urease to decompose bioavailable urea for autonomous propulsion, whereas an internal microbubble serves as an ultrasound imaging contrast agent for deep tissue imaging and navigation. Magnetic nanoparticle integration enables imaging-guided magnetically controlled motion and catalase functionalization facilitates chemotactic movement towards hydrogen peroxide gradients, directing robots to tumour sites. Focused ultrasound triggers robot shell collapse and inertial cavitation of the released microbubbles, creating mechanical forces that enhance therapeutic payload penetration. In vivo studies validate the tumour-targeting and therapeutic efficacy of these robots, demonstrating enhanced antitumour effects. This multifunctional microbubble robotic platform has the potential to transform medical interventions and precision therapies.

Dysfunctions of the endometrium, the uterus inner lining, can impair embryo implantation and reduce pregnancy rates. Intrauterine administration of cytokines has shown potential to improve endometrium function, but it is challenged by poor targeting and dose-limiting systemic side effects. Here we present a strategy for introducing therapeutic messenger RNA into the endometrium for the treatment of reproductive disorders. mRNA was loaded into a ligand-conjugated lipid nanoparticle (LNP), enabling multivalent interactions with the temporally overexpressed integrin receptors on the endometrial surface during the window of implantation. Conjugating the targeting ligand directly to the lipid component enhanced endometrial protein expression after intrauterine infusion and reduced systemic expression in the liver and spleen. A single infusion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA-loaded LNP sustained local protein expression for several hours and reduced GM-CSF systemic exposure. In a murine model of endometrial injury, GM-CSF mRNA-loaded LNP improved embryo implantation rates, outperforming recombinant GM-CSF. Our strategy demonstrates the efficacy of using mRNA to improve fertility outcomes.