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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

Multi-drug nanotherapy consistently outperforms single-drug therapy, multi-drug combination therapy, and single-drug nanotherapy across different experimental settings, therapy strategies and cancer types.

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.

A bioinspired microneedle patch mimics the natural rhythm of human growth hormone secretion by combining burst-release and delayed-release modules to promote improved bone growth in mice and rats.

Hypoglycemia is a serious and potentially life-threatening condition for people with insulin dependent diabetes, but preventative hypoglycemia therapies are elusive. Here, the authors report the use of catechol and boronic acid chemistry to design a self-crosslinkable hydrogel-based microneedle patch that delivers Zinc-Glucagon at low glucose levels and prevents insulin-induced hypoglycemia.

The dissatisfied delivery efficiency of drugs to lungs and other metastatic sites limit the corresponding therapeutic efficacy. Here this group reports an inhalable surfactant-based nanoliposome system to co-deliver Osimertinib and DNA plasmid which is capable of fusing into pulmonary surfactant, penetrating through physiological barriers and targeted accumulating in lung tissues.

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.

This work compares the preclinical lung biodistribution and efficacy profile of inhaled anti-CCN2 (cellular communication network factor 2) Anticalin® protein PRS-220 for the treatment for idiopathic pulmonary fibrosis (IPF) compared to systemic delivery of a CCN2 inhibitor.

This study reports on self-aggregating injectable microcrystals for administering long-acting drug implants via low-profile needles, a key factor in patient adoption. Microcrystal self-aggregation is engineered through a solvent exchange process to form depots with minimal polymer excipient, demonstrating enhanced long-term release of a model contraceptive drug in rodents.

Middle-aged individuals are more susceptible to obesity, but the mechanisms are unclear. Here, the authors show that extracellular vesicles from adipose progenitor cells in middle-aged individuals lack miR-145-5p, driving inflammation, and that restoring miR-145-5p could prevent midlife obesity.

STING agonist-based endoplasmic reticulum-targeting molecules can be conjugated directly onto antigens to deliver them to the cross-presentation pathway, improving CD8⁺ T cell responses against tumours and viruses.

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.

Delivering RNA therapies to the brain is challenging due to the blood-brain barrier. Here, the authors show in murine models that a berberine-inspired lipid nanoparticle system enhances brain targeting via dopamine D3 receptors, enabling effective treatment for neurological diseases.

Nanocarriers can be used for accurate tumor targeting, but their limited water solubility impedes the stable storage and poses biosafety risks in clinical translation. Here, the authors report water-soluble carbon quantum dots that show stability toward long-term storage and the addition of electrolytes, as well as negligible protein adsorption, immunogenicity, hemolytic activity and toxicity.

This study presents the development of nanodrugs based on bacterial-derived outer membrane vesicles for targeted intervention in nerve–cancer crosstalk, which efficiently enhances pancreatic cancer chemotherapy.

Treating myocardial reperfusion injury via nanotherapy is challenging due to clearance by the mononuclear phagocyte system. Here, the authors target the spleen to reduce acute heart injury and improve long-term cardiac function via transient IRF7 inhibition.

This article presents a polymeric membrane-enclosed insulin crystal equipped with physiological signal-sensing microdomains, dubbed ‘smart drug crystals’, that enables long-term, glucose- and β-hydroxybutyrate-dually responsive drug release for type 1 diabetes therapy.

Treatment of the chronic disease ulcerative colitis is impeded by systemic side effects of orally administered drugs. Here the authors develop a gel that uses the rectal temperature as a mechanism to trigger solidification for localized delivery of colitis therapeutics.

The photobleaching property of heptamethine cyanine enables efficient charge conversion of nanoparticles. Here heptamethine-cyanine-based nanoparticles achieve specific tumour imaging, deep tumour penetration and high therapeutic efficacy in rectal cancer animal models.

Uricase-based gout treatments are generally limited due in part to the accumulation of H₂O₂ in an arthrosis microenvironment. Here the authors develop a nanomotor-based strategy that simultaneously degrades uric acid and eliminate H₂O₂ for efficient gouty therapy.

Genetically engineered commensal bacteria are promising living drugs, however, drug delivery is limited to bacterial colonization site. Here, the authors report an oral protein delivery technology utilizing an engineered bacterial type zero secretion system (T0SS) via outer membrane vesicles (OMVs).

Controlled synthesis of supramolecular structures within lysosomes holds promise for cancer imaging and treatment. The authors introduce a programmable assembly strategy to generate fluorescent nanofibres in tumour cell lysosomes, enabling targeted tumour accumulation and inducing pyroptosis for precise cancer imaging and immunotherapy.

Transferrin receptor (TfR) and CD98hc are increasingly used to enable more effective drug delivery to the central nervous system. Here, the authors reveal comprehensive and distinct brain cellular and whole body biodistribution patterns of TfR- and CD98hc-binding molecules.

The stability and delivery of biopesticides limits application. Here, azadirachtin is co-assembled with plant secondary metabolites for efficient drug delivery, demonstrating pest management, the activation of plant defensive capacity, while increasing the production yield of crops.

The intravenous injection of oxygen via polymeric microbubbles that are stable in storage yet quickly dissolve following intravenous injection led to the maintenance of critical oxygenation and to improved survival in swine with profound hypoxaemia.

Here, authors looked at the roles of Kupffer cells in determining intrahepatic traffic of PEGylated liposomal doxorubicin, providing information for design and clinical applications of liposomal therapeutics.

Local anesthetic sustained release systems suffer from untriggered rapid drug release upon application. Here the authors overcome this issue by covalently linking tetracaine to a polymer gel via a photo-cleavable linkage, enabling light-triggered and repeatable drug release.