Engineered Biomimetic Nanovesicles Derived From Bone Marrow Stromal Cells With Innate Homing Capability for Targeted Delivery.

Precise delivery of pharmaceuticals administered to bone marrow for various bone diseases is challenging, given the bone marrow-blood barrier (MBB). Bone marrow stromal cells (BMSCs) derived from bone marrow can naturally infiltrate the MBB and home to bone tissue. Here, biomimetic nanovesicles (namely mNVs) engineered with the extracted cell membrane from BMSCs are reported for homing delivery of different core nanomedicines to bone marrow.

Diamond-Inspired DNA Hydrogel Based on Tetrahedral Framework Nucleic Acids for Burn Wound Healing.

Burn wounds frequently pose high risks of a prolonged healing process and even death due to the persistent reactive oxygen species (ROS)-mediated inflammatory cascade. There is an urgent requirement for advanced dressings modulating the immune microenvironment surrounding the wound. DNA hydrogels have been preliminarily investigated in tissue regeneration due to their excellent permeability, editability, and biocompatibility.

Tetrahedral Framework Nucleic Acid Composite Hydrogel Loaded with Naringin for Full Alveolar Bone Regeneration.

The complexity of the endogenous tissue structure and exogenous healing environment complicates the study of alveolar bone regeneration in regenerative medicine. Naringin (Nar), a flavonoid monomer found in traditional Chinese medicines, induces osteogenesis in bone marrow mesenchymal stem cells (BMSCs) and therefore is well suited for bone injury treatment. However, the clinical applications of Nar are limited by its low bioavailability and room-temperature solubility in water.

A Sprayable Nucleic Acid Hydrogel for Diabetic Wound Healing via Immunomodulation and Angiogenesis.

Diabetic wounds (DWs), a prevalent form of chronic wound, are highly susceptible to infection and impaired healing due to immune dysregulation, persistent inflammation, and abnormal angiogenesis, which can ultimately result in increased disability, mortality, and healthcare burdens. Uncontrollable bleeding and coagulation disorders following severe trauma present major challenges for existing hemostatic agents. To address these issues, a multifunctional nucleic acid hydrogel (TR21@TS) is developed by integrating microRNA-21-5p-loaded tetrahedral framework nucleic acids (tFNAs) with tannic acid (TA) and tetra-polyethylene glycol (4-PEG) derivatives, and the hybrid hydrogel exhibited wet adhesiveness, mechanical robustness, sprayability, and injectability.

Advances in microneedle technology for skin wound healing: integrating nanomaterials and intelligent drug delivery systems.

Recent clinical challenges in wound healing, particularly chronic non-healing wounds such as diabetic ulcers and burn injuries, highlight the limitations of current treatments in achieving rapid healing, infection control, and scar reduction. The integration of nanomaterials with microneedle technology-an emerging platform for transdermal drug delivery and microenvironment regulation-offers significant advantages in addressing these challenges. By incorporating functional nanomaterials such as nanonzymes, metal nanoparticles, and antimicrobial nanostructures, microneedle platforms enhance local hemostasis, infection suppression, inflammation regulation, angiogenesis, and tissue regeneration.

Potential Applications of Multifunctional Tetrahedral Framework Nucleic Acids in Bone Tissue Engineering.

Though bone defects are common, treating critical-sized bone defects remains a significant clinical challenge. A potential strategy for bone repair that avoids the need for autogenous bone grafts is bone tissue engineering (BTE). Recently, BTE strategies incorporating vascularization, neurorestoration, and immunomodulation of bone substitutes are regarded as a comprehensive and promising method for bone repair.

Rib-indexed quantitative lung ultrasound versus chest X-ray for lung recruitment assessment in neonates with moderate-severe ARDS on surfactant therapy combined with prone position: a prospective observational study.

Serial lung recruitment assessment in neonates with moderate-to-severe neonatal acute respiratory distress syndrome (NARDS) is crucial. However, current methods involve ionizing radiation or invasiveness, which limits their serial use in neonates. This study evaluated the feasibility of rib-indexed quantitative lung ultrasound (LUS) as a radiation-free alternative for monitoring lung aeration in neonates with moderate-to-severe NARDS on surfactant therapy combined with prone position.

DNA Tetrahedron Functionalized Microneedles Blocking IL-6 to Promote Skin Wound Healing.

Excessive secretion of Interleukin-6 (IL-6) is a critical barrier to the healing of inflammatory wounds. Previous attempts aimed to overcome this challenge by using antibodies to neutralize IL-6. However, the immunogenicity of an antibody may trigger antidrug antibody formation, resulting in reduced therapeutic efficacy and possible adverse reactions.

Framework Nucleic Acid Nanomaterials for Central Nervous System Therapies: Design for Barrier Penetration, Targeted Delivery, Cellular Uptake, and Endosomal Escape.

Therapeutic development for central nervous system (CNS) disorders remains hindered by inefficient drug penetration across the blood-brain barrier (BBB) and a lack of spatiotemporal precision targeting. Conventional nanocarriers face challenges such as structural heterogeneity, off-target effects, and limited BBB traversal, compromising clinical efficacy. Framework nucleic acid (FNA) nanomaterials, characterized by atomic-level precision, programmable self-assembly, and inherent biocompatibility, present a transformative platform to overcome these barriers.

Oral Administration of a Tetrahedral Framework DNA-Based Nanoshot Attenuates Liver Fibrosis via Targeting Galectin-3.

Liver cirrhosis is a prevalent global health issue that has imposed a significant economic burden. Currently, there is a lack of effective treatment for liver cirrhosis due to poor patient compliance with injectable medications. Hepatic uncontrolled inflammation is the primary therapeutic target for liver cirrhosis.

Flexible Delivering Potential of Oligonucleotides Reconstructed DNA Tetrahedron.

Tetrahedral framework nucleic acid (tFNA), a 3D nanostructure formed by four single-stranded DNAs (ssDNAs), has shown great application potential for excellent editability, good biocompatibility, abundant bio-functions, and superior drug loading capacity. However, mismatching and self-agglomeration of tFNA composition structure have affected its yield and bioavailability. To address these issues, one chain of tFNA is re-programmed into three short-chain oligonucleotides, and then self-assembled with the remaining three chains to form a DNA tetrahedron (oligonucleotides reconstructed DNA tetrahedron, ORT).

Neomycin loaded by tetrahedral framework nucleic acids enhances antimicrobial sensitivity against bacteria.

Burn wound infections pose significant challenges to the management of burn injuries. Antibiotic therapy now is playing a crucial part in preventing and treating post-burn infections. Neomycin sulfate (NeoS; one of the most commonly used antibiotics for treating multiple bacterial infections) faces limitations such as low bioavailability and severe side effects.

3,3'-Diindolylmethane Ameliorates Metabolism Dysfunction-Associated Fatty Liver Disease via AhR/p38 MAPK Signaling.

: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic hepatic condition marked by lipid buildup, lipotoxicity, and inflammation. Prior research indicates that 3,3'-Diindolemethane (DIM), a natural indole-type phytochemical that is abundant in brassicaceae vegetables, has been reported to reduce body weight and improve lipid metabolism in mice subjected to a high-fat diet (HFD). The aryl hydrocarbon receptor (AhR), a nuclear receptor implicated in lipid metabolism and immune regulation, serves as a functional receptor for DIM.

Protection of Framework Nucleic Acid Complexes via Regulating Ferroptosis on Myocardial Ischemia-Reperfusion Injury.

The pathogenesis of myocardial ischemia-reperfusion injury (MIRI) is a complex process involving multiple pathophysiological mechanisms, including mitochondrial dysfunction, oxidative stress, and ferroptosis. Therefore, MIRI continues to pose a significant obstacle in cardiovascular therapy. Curcumin (Cur), a natural polyphenolic compound with potent antioxidant and antiferroptosis properties, has therapeutic potential but is poorly soluble, unstable, and has low bioavailability.

Multi-Route Administration Delivery System Based on Tetrahedral Framework Nucleic Acids for Alleviating Type I Hypersensitivity Reactions.

Type I hypersensitivity reactions are the most common type of hypersensitivity reactions and can cause various symptoms in different body systems. Currently, there is no standard treatment for the different manifestations of type I hypersensitivity reactions at different sites. To address this challenge, a nanocomposite named tFNAs-siRNA-siRNA (TSS) is designed based on tetrahedral framework nucleic acids (tFNAs).

Transient intracellular expression of PD-L1 and VEGFR2 bispecific nanobody in cancer cells inspires long-term T cell activation and infiltration to combat tumor and inhibit cancer metastasis.

Background: PD-L1, an immune checkpoint inhibitor, and VEGFR2, essential for cancer metastasis, play pivotal roles in tumorigenesis. However, their miniature bispecific intracellular nanobodies for combining check-point blockade and anti-metastasis anticancer therapy remain underexplored.

Methods: The intrabodies were developed using gene cloning technology.

A Noninvasive Nanoeyedrop Therapy for the Inhibition of Uveal Melanoma: Tetrahedral Framework Nucleic Acid-Based Bioswitchable MicroRNA Delivery System.

Uveal melanoma (UM) is the most prevalent primary intraocular malignancy, exhibiting pronounced invasive characteristics and a dismal prognosis. Conventional therapeutic modalities, including radiotherapy, laser therapy, and surgery, are frequently invasive and can lead to complications, underscoring the need for the development of efficacious, safe, and noninvasive therapeutic approaches. This study investigated a tetrahedral framework nucleic acid (tFNA)-based bioswitchable microRNA (miRNA) delivery system, designated BiRDS, engineered for the inhibition of UM through the use of miRNA suppressors via noninvasive eyedrops.

Cartilage-Penetrating Framework Nucleic Acid Nanoparticles Ameliorate Osteoarthritis by Promoting Drug Delivery and Chondrocyte Uptake.

Osteoarthritis (OA) is a chronic joint disease that causes a gradual deterioration of articular cartilage. A major challenge in OA treatment is the limited penetration and delivery efficiency of drugs to cartilage and chondrocytes due to the rapid clearance of drugs through synovial fluid in joints and the osmotic barrier of the cartilage extracellular matrix (ECM). To address this issue, a novel tetrahedral framework nucleic acid (tFNA)-based nanomedicine delivery system (tFNA-2WL) is first synthesized with excellent cartilage permeability and perfect chondrocyte endocytosis properties.

Application of point-of-care ultrasound-guided tip navigation combined with visualised directional high-frequency linear array probe compression to improve the success rate of umbilical venous catheterisation in critical neonates: protocol of a multicentre randomised controlled trial in neonatal units.

Introduction: Conventional umbilical venous catheterisation (UVC) relies on 'blind' insertion without ultrasound guidance, resulting in low success and high complication rates. While point-of-care ultrasound (POCUS)-based tip navigation and location has improved this scenario by enabling real-time visualisation of the catheter tip during UVC, challenges remain when the catheter is inadvertently inserted into an incorrect vessel. Selecting effective intervention methods to correct the catheter direction has become a key research focus.

Targeted siRNA Delivery Against RUNX1 Via tFNA: Inhibiting Retinal Neovascularization and Restoring Vessels Through Dll4/Notch1 Signaling.

Purpose: To assess the efficacy of tetrahedral framework nucleic acids (tFNAs) as a delivery system for small interfering RNA (siRNA) targeting RUNX1 (siRUNX1) in inhibiting retinal neovascularization (RNV) and restoring vascular integrity via the Dll4/Notch1 signaling pathway.

Methods: tFNAs and tFNAs-siRUNX1 were synthesized using annealing of single-stranded DNAs and characterized by PAGE and high-performance capillary electrophoresis. Human umbilical vein endothelial cells were treated under hypoxic conditions with tFNAs-siRUNX1, and cellular uptake was evaluated using fluorescence microscopy and flow cytometry.

Current Understanding and Translational Prospects of Tetrahedral Framework Nucleic Acids.

Tetrahedral framework nucleic acids (tFNAs) represent a promising advancement in nucleic acid nanotechnology due to their unique structural properties, high biocompatibility, and multifaceted biomedical applications. Constructed through a one-pot annealing method, four single-stranded DNAs self-assemble into stable, three-dimensional tetrahedral nanostructures with enhanced mechanical robustness and physiological stability, resisting enzymatic degradation. Their ability to permeate mammalian cells without transfection agents, coupled with modifiable surfaces, positions tFNAs as versatile carriers for drug and gene delivery systems.

Tetrahedral-DNA-Nanostructure-Modified Engineered Extracellular Vesicles Enhance Oral Squamous Cell Carcinomas Therapy by Targeting GPX4.

Oral squamous cell carcinoma (OSCC) represents a heterogeneous group of malignancies originating from the mucosal lining of the oral cavity. Current treatment modalities primarily involve surgery, chemotherapy, and radiotherapy. Despite the use of multimodal therapy, the 5 year overall survival rate for OSCC remains around 50%, underscoring the need for the development of nontoxic agents with potent antitumor activity.

Nanoparticles encapsulating antigenic peptides induce tolerogenic dendritic cells in situ for treating systemic lupus erythematosus.

Using Tetrahedral framework nucleic acids, we combined antigenic peptides to create the "DART" vaccine: DNA framework-Antigenic peptide-RNA modification-Targeting aptamer coupling. Generating antigen-specific tolerogenic dendritic cells (tolDCs), for systemic lupus erythematosus (SLE) is a potential therapeutic strategy for addressing compromised autoimmune tolerance. However, simple antigenic peptides degrade easily, lack specificity for delivery to dendritic cells (DCs), and cannot transform DCs to tolDCs.

BBPs-functionalized tetrahedral framework nucleic acid hydrogel scaffold captures endogenous BMP-2 to promote bone regeneration.

Bone Morphogenetic Protein-2 (BMP-2) is a key growth factor for inducing osteogenic differentiation and promoting bone remodeling. However, the exogenous application of delivery systems for BMP-2 has been hampered by various postoperative complications, poor stability and high price. Hence, in situ enrichment of endogenous BMP-2 is promising.