Search

Diabetic wounds are a prevalent type of chronic wound that is challenging to treat due to the dynamic and complex wound microenvironment. Here, Cong et al. presents a dimeric copper peptide incorporated hydrogel for multifunctional treatment of diabetic wounds.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Depletion of circulatory asparagine (Asn) by L-asparaginase (ASNase) has been used for clinical treatment of leukemia. Here this group develops core-shell structured cascade-responsive nanoparticles for sequential modulation of exogenous Asn supply and endogenous Asn production, thereby achieving the amino acid depletion therapy against solid tumors.

On-target, off-tumour toxicity is a major concern in immunotherapy. Here, aided by computer docking analysis, the authors introduce a single oxygen atom into the TLR7/8 agonist R848, generating a radiotherapy-activatable prodrug agonist that in mice helps mitigate systemic toxicity while triggering effective anti-tumor immunity responses upon radiation.

Ferroptosis immunotherapy is promising for treating triple-negative breast cancer, but hindered by limited iron levels in tumor cells and a lack of specific immune responses. Here, the authors report a biohybrid system that enhances iron level by activating endogenous iron ions and replenishing exogenous iron ions and targets ferritin for synergistic ferroptosis immunotherapy.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

In this work the authors develop PACES (protein-assembly complex for elimination system) which uses cell-selective nanofibers with bioorthogonal decoration of an E3 recruiter to trap and degrade proteins. This strategy complements PROTACs and PPI-based approaches, expanding the degradable proteome.

The development of subunit vaccines mimicking the molecular complexity of attenuated vaccines has been limited by the difficulty in co-delivery of multiple chemically diverse payloads. Here, the authors report hierarchical hydrogels, assembled from a single homopolymer via a multi-stage process, that enable ratiometric loading of a protein antigen and four physicochemically distinct adjuvants.

Poly(carboxybetaine) lipids enhance mRNA lipid nanoparticles efficacy and reduce their immunogenicity, being promising alternatives to poly(ethylene) glycol lipids used in traditional mRNA lipid nanoparticle formulations.

Intracellular siRNA delivery is key for RNAi therapy. Here, the authors report on bioengineered nanovesicles with tumour cell-targeting and enzyme-activated membrane fusion functions for efficient cytosolic siRNA delivery to knockdown oncogenes, leading to effective tumour gene therapy.

Excessive fibrosis triggered by bisphosphonates impairs fracture healing in osteoporotic bone. Here, the authors develop an injectable magnesium-alendronate MOF-based hydrogel adhesive and show it prevents fibrosis and enhances bone repair, improving healing strength in an osteoporotic rat model.

Steroid resistant asthma can be combatted with antibody therapy, but delivery and off-target effects are a concern. Here, the authors report on the co-delivery of thymic stromal lymphopoietin nanobody mRNA and budesonide in budesonide-incorporated inhalable lipid nanoparticles to treat steroid resistant asthma.

Screening of DNA-encoded chemical libraries against prostatic acid phosphatase yielded OncoACP3, a modular small organic ligand with picomolar binding affinity that enabled targeted payload delivery to prostate cancer.

End-of-life nonhuman primates can be used to screen pools of lipid nanoparticles for clinical safety studies.

NICER is a broad-spectrum nanovaccine based on a nanovesicle system that can induce an effective immune response via epigenetic regulation to target both cancer stem-like cells and bulk tumour cells to prevent tumour recurrence.

Long-circulating, transfection-competent LNP-mRNA systems are key for effective extrahepatic delivery. Here, authors show that LNPs with high bilayer lipid ratios yield high mRNA encapsulation, prolonged circulation, and enhanced transfection in extrahepatic tissues.

Modifying the polyethylene glycol lipid ratio and phospholipids in the lipid nanoparticle component of nucleoside-modified mRNA–lipid nanoparticle vaccines is shown to have an impact on the elicited cellular and humoral immune responses.

Lipid nanoparticles (LNPs) delivering mRNA after intratumoral administration could be a promising cancer treatment strategy. Here this group reports the intratumoral delivery of mRNA with LNPs inducing the expression of purine nucleoside phosphorylase and inhibiting the progression of head and neck squamous cell carcinoma in vivo.

Effective delivery of therapeutic agents to the infection site and the modulation of the immunosuppressive microenvironment at the site of infection are vital for the treatment of chronic bacterial infections but remain elusive. Here, the authors address these issues by developing a nanomedicine that combines chemical and immunological therapies for chronic bacterial infection management.

Han et al. report the design and characterization of a pressure-fused biomineral tablet for the long-acting sustained release of IL-2, promoting antitumor immune responses in preclinical models of melanoma.

Chemotherapy is an important treatment for glioblastoma, but its effect is limited by the blood-brain barrier (BBB) and complex tumor microenvironment. Here, the authors address these issues by developing a Trojan horse-inspired nanobot system (Trojanbot) combining chemokine-guided neutrophil transport across the BBB with enzyme-driven nanobots that penetrate tumors via H₂O₂ gradients.

Stomata are key entry points for plant pathogens. Here, the authors engineer stomata-targeted nanoparticles to reduce bacterial colonization while preserving stomatal function, enabling a more precise strategy to enhance crop defence.

Exosomes have huge potential for drug delivery, but drug loading can be difficult. Here, the authors report on fusogenic lipid nanoparticles which, when mixed with exosomes rapidly fuse, non-destructively loading large drugs without compromising exosome biological functions, and demonstrate neurological application.

Microwave-assisted tumour-derived microparticles enhance antitumour activity, safety and drug delivery, outperforming traditional ultraviolet-derived methods.

Here, based on single-pass intestinal perfusion platform, the authors establish a microbiota-based drug permeability screening framework to compare perfusion and metabolomic profiles of 32 orally administered drugs in germ-free rats, and show that increased permeability of N-Acetylcysteine is mediated by cysteine-3-ketosphinganine of Bacteroides.

Cryoprotectants are needed for the storage of lipid nanoparticles (LNPs). Here, the authors report on a study which shows that freezing can be harnessed to reformulate LNPs in a way that both preserves their integrity and boosts mRNA delivery after sub-zero storage by increasing endosomal escape.

A collagenase nanogel backpack enhances CAR-T cell therapy in pancreatic cancer by improving cell infiltration and overcoming physical barriers, enabling potent tumour regression and prolonged survival.

Engineered pyroptotic vesicles formed during tumour cell pyroptosis and engineered as personalized tumour vaccines can activate a robust antitumour immune response for post-surgical tumour recurrence inhibition.

Tumour endothelial cell macropinocytosis is the dominant mechanism for nanoparticle entry into the tumour. Enhanced nanoparticle tumour accumulation may be due to upregulated macropinocytosis membrane ruffling compared with most healthy tissues.

Natural vesicles typically consist of a lipid membrane enclosing substances. Now a coacervate vesicle formed by liquid–liquid phase separation of cholesterol-modified DNA and histones has been developed. Unlike traditional vesicles, these lack a membrane and feature a high-density liquid layer around a water-filled cavity, offering enhanced kinetic stability and potential as a biopharmaceutical delivery system.

This study identifies FABP4 as driver of postmenopausal osteoporosis and shows that targeting FABP4 with a small-molecule inhibitor or bone-targeted nanoparticles can reduce bone loss and offers a potential new treatment approach.

Genetic vaccines can be quickly formulated and tested but require multiple administrations to generate a durable antibody response, as in the case of protein subunit vaccines. Here SpyTag/SpyCatcher technology is used to develop a genetic vaccine encoding antigen-displaying capsid virus-like particles to enhance the immune response against the Pfs25 malaria antigen.

Endosomal escape is the major limitation in LNP delivery efficency. Here, the authors report on endosomolytic chloroquine-like lipid nanoparticles for mRNA delivery and genome editing by integrating the chloroquine scaffold into ionizable lipids, demonstrating improved transfection in vivo.

The efficacy of anticancer gene therapy varies by the delivery efficiency of the mRNA cargo as well as their injection method. Here this group reports using LNP-delivered mRNA encoding 3 C protease treated on three different types of solid tumor models showing effective tumor growth inhibition, with three different injection methods, respectively.

Dendritic cell-based therapies have been exploited as immunotherapeutic approaches for cancer treatment. Here the authors report a platform integrating antigen-capturing nanoparticles and type 1 conventional dendritic cells for in situ cancer immunization, promoting anti-tumor immunity in preclinical models.

Encapsulation of large-size DNA molecules into lipid nanoparticles (LNPs) remains challenging. Here, the authors engineer PEGylated LNPs with DNA and plasma proteins to improve the delivery of large DNA molecules, enhancing the gene therapy potential.

Reaching the depths of the respiratory tract is hard even with vapor-based drug delivery. Here, the authors devise inhalable biohybrid microrobots that, thanks to their motility, reach deeper regions of the lungs.

Liver macrophages are a major obstacle to extrahepatic drug delivery. This study identifies the receptor–ligand interactions that they use to capture circulating nanoparticles and leverages this understanding to engineer nanoparticles that escape macrophage uptake.

Rigid wearable and implantable bioelectronic devices present mechanical mismatches with soft biological tissues that limit their applicability. This Review systematically outlines materials and integration strategies for soft bioelectronic devices that overcome this mismatch and have the potential to enable continuous health monitoring, therapeutic interventions and closed-loop healthcare.

RNAi therapies have potential to treat a range of diseases including liver fibrosis. Here, the authors report on the delivery of miR-325-3p in nucleic acid spheres, which can enter the liver sinusoidal endothelial cells, reversing their capillarisation, treating liver fibrosis in mice.

Nitric oxide reversibly breaches vascular basement membrane barriers, facilitating nanoparticle penetration into the tumour interstitium through explosive eruptions.

Tracking biomolecules in living cells requires fast but gentle labeling. Here, authors introduce inCu-click, a DNA-conjugated ligand that localizes copper to enable efficient intracellular CuAAC, allowing live-cell fluorescent labeling of lipids and proteins without toxicity.

Coarctate reactions, involving the simultaneous formation and cleavage of two bonds at single or multiple atoms, have remained largely unexplored for biomolecular applications. Here, the authors use an azo-ene-yne coarctate reaction to synthesize isoindazole-based N-heterocycles and explore their applications in the synthesis of unnatural amino acids and drug conjugates, and late-stage peptide functionalization.

Methods of damaging cancer cells are of therapeutic interest. Here, the authors report on using gold nanoparticles as electron sinks with electroactive bacterial membranes to disrupt cancer cell redox balance, electron transfer induces oxidative stress and triggers cell death by apoptosis.

As the field of engineered therapeutic living cells advances, new strategies to deliver them into the body are needed. This Review identifies current challenges in living medicine delivery and discusses how biomaterial strategies could be leveraged to overcome these clinical barriers.

Development of safe and effective non-viral delivery systems is important for broadening clinical applications of mRNA delivery. Here, Vlasova et al. create a library of ionizable lipopolymers using split-Ugi reaction to develop nanoparticles for targeted pulmonary delivery of mRNA.

A highly mobile adeno-associated virus with high tropism for pulmonary arterial smooth muscle cells prevents and reverses the development of pulmonary arterial hypertension in mice and rats.