N 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
N Nature Nanotechnology · Sep 24, 2025 Meso–macroporous hydrogel for direct litre-scale isolation of extracellular vesicles Extracellular vesicles are cell-originated lipid bilayer membrane vesicles that play vital roles in cell-to-cell communications. While extracellular vesicles hold substantial biomedical potential, conventional methodologies for isolating extracellular vesicles require elaborate preprocessing and, therefore, remain labour intensive and limited by throughput. To overcome these challenges, we present a facile fabrication route for generating a meso–macroporous hydrogel matrix with pores of ~400 nm for customizable extracellular vesicle isolation. By combining surface charge-selective capture of extracellular vesicles within the hydrogel matrix and their recovery by high ionic strength, we report direct extracellular vesicle isolation with a throughput range from microlitre to litre scales, without preprocessing, for various biofluids, including whole blood, plasma, ascites, saliva, urine, bovine milk and cell culture media. Furthermore, we demonstrate that the meso–macroporous hydrogel also serves as a solid-phase matrix for preserving extracellular vesicles for on-demand downstream analyses, making it applicable for therapeutics, cosmeceuticals and disease diagnostics. Biomaterials Biomedical engineering Characterization and analytical techniques Nanopores Synthesis and processing Cell Biology Proteomics Drug Development Clinical
N Nature Nanotechnology · Sep 10, 2025 Nanofibrous supramolecular peptide hydrogels for controlled release of small-molecule drugs and biologics Maintaining safe and potent drug levels in vivo is challenging. Multidomain peptides assemble into supramolecular hydrogels with a well-defined, highly porous nanostructure that makes them attractive for drug delivery. However, their ability to extend release is typically limited by rapid drug diffusion. Here, to overcome this challenge, we present self-assembling boronate ester release (SABER) multidomain peptides capable of engaging in dynamic covalent bonding with payloads containing boronic acids. As examples, we demonstrate that SABER hydrogels can prolong the release of boronic acid-containing small-molecule drugs and boronic acid-modified biologics such as insulin and antibodies. Pharmacokinetic studies reveal that SABER hydrogels extend the therapeutic effect of ganfeborole from days to weeks, preventingMycobacterium tuberculosisgrowth compared with oral administration in an infection model. Similarly, SABER hydrogels extended insulin activity, maintaining normoglycemia for 6 days in diabetic mice after a single injection. These results suggest that SABER hydrogels present broad potential for clinical translation. Biomedical engineering Drug delivery Molecular self-assembly Supramolecular polymers Drug Development Mouse Clinical
