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.

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.

Designed biomolecular condensates are emerging condensed-phase assemblies, initially conceived to mimic cellular biomolecular condensates for use in biology-inspired applications such as delivery and storage of biomolecules. In recent years, rational design approaches informed by supramolecular chemistry and biomolecular nanotechnology, including the use of peptide and DNA nanotechnology for building-block minimalization and site-specific interactions, have evolved rapidly, going beyond the molecular basis of cellular condensates in terms of both composition and functionality. Thus, synthetic condensates are designed from diverse molecular building blocks, including single- or multicomponent polypeptides, peptides, RNA, DNA or biopolymers; moreover, their applications are continuously evolving to encompass new nanotechnology-relevant functions including biosensing and bioadhesion, where condensates offer advantages such as responsiveness, programmability and molecular compartmentalization. In this Review, we show the main concepts behind the molecular design of synthetic condensates, from biological mimicry to purely synthetic approaches. We discuss the mechanisms that allow control and regulation of condensate properties and the remaining challenges in analysing these properties. Finally, we discuss the applications of synthetic condensates thus far, the potential in leveraging condensates as platforms for nanotechnological applications, and the remaining hurdles towards realizing this promise. We also provide an overview of the patent landscape, highlighting trends in commercial development across areas such as delivery systems, microreactors and sensing technologies.

Despite the considerable success of clinically approved immune-based therapies for treating advanced melanoma, a significant fraction of patients are not responsive owing to mechanisms engaged by the tumour to evade the immune system. Here we report the surprising finding that a clinically validated and tunable self-therapeutic ultrasmall silica nanoparticle prolongs survival in a highly resistant melanoma model in combination with interleukin-6 and PD-L1 inhibition through activation of the stimulator of interferon genes/interleukin-6/PD-L1 axis and reprogramming of the tumour microenvironment towards a pro-inflammatory phenotype. In a murine model, induction of significant cytotoxic and antitumour inflammatory responses leads to differential activation of immune cell populations in a CD8-dependent manner via type I/II interferon pathways after systemic particle injection. Importantly, these immunostimulatory responses accompany significant reductions in cell populations and receptors driving suppressive activities. Mechanistic insights highlight the potential clinical utility of this platform to maximize antitumour immunity and efficacy by subverting suppressive components in the tumour microenvironment.