A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Фев. 29, 2024

Abstract Diabetic osteoporosis (DOP) is a significant complication that poses continuous threat to the bone health of patients with diabetes; however, currently, there are no effective treatment strategies. In diabetes, increased levels ferroptosis affect osteogenic commitment and differentiation mesenchymal stem cells (BMSCs), leading skeletal changes. To address this issue, we aimed target propose novel therapeutic approach for DOP. We synthesized ferroptosis-suppressing nanoparticles, which could deliver curcumin, natural compound, marrow using tetrahedral framework nucleic acid (tFNA). This delivery system demonstrated excellent curcumin bioavailability stability, as well synergistic properties tFNA. Both in vitro vivo experiments revealed nanoparticles enhance mitochondrial function by activating nuclear factor E2-related 2 (NRF2)/glutathione peroxidase 4 (GPX4) pathway, inhibiting ferroptosis, promoting BMSCs diabetic microenvironment, reducing trabecular loss, increasing formation. These findings suggest curcumin-containing DNA tetrahedron-based have promising potential DOP other ferroptosis-related diseases.

Язык: Английский

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DNA framework signal amplification platform-based high-throughput systemic immune monitoring

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 7, 2024

Abstract Systemic immune monitoring is a crucial clinical tool for disease early diagnosis, prognosis and treatment planning by quantitative analysis of cells. However, conventional using flow cytometry faces huge challenges in large-scale sample testing, especially mass health screenings, because time-consuming, technical-sensitive high-cost features. the lack high-performance detection platforms hinders development high-throughput technology. To address this bottleneck, we constructed generally applicable DNA framework signal amplification platform (DSAP) based on post-systematic evolution ligands exponential enrichment tetrahedral framework-structured probe design to achieve high-sensitive diverse cells, including CD4+, CD8+ T-lymphocytes, monocytes (down 1/100 μl). Based advanced platform, present novel immune-cell phenotyping system, DSAP, achieving 30-min one-step without cell washing subset showing comparable accuracy with while significantly reducing time cost. As proof-of-concept, DSAP demonstrates excellent diagnostic immunodeficiency staging 107 HIV patients (AUC > 0.97) within 30 min, which can be applied infection screening. Therefore, initially introduced promising open robust routes point-of-care device development.

Язык: Английский

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Multifunctional MXene-Based Bioactive Materials for Integrated Regeneration Therapy

ACS Nano, Год журнала: 2023, Номер 17(20), С. 19526 - 19549

Опубликована: Окт. 7, 2023

The reconstruction engineering of tissue defects accompanied by major diseases including cancer, infection, and inflammation is one the important challenges in clinical medicine. development innovative strategies such as multifunctional bioactive materials presents a great potential to overcome challenge disease-impaired regeneration. As representative two-dimensional nanomaterials, MXenes have shown physicochemical properties been diffusely studied multimodal nanoplatforms field biomedicine. This review summarized recent advances integrated regeneration-therapy applications MXene-based biomaterials, regeneration-tumor therapy, regeneration-infection regeneration-inflammation therapy. recognized good candidates for promoting regeneration treating through photothermal regulating cell behavior, drug gene delivery. current future perspectives biomaterials are also discussed well this review. In summary, promising disease treatment due their favorable functions. However, there still many obstacles that must be addressed understanding mechanism, ensuring long-term biosafety, improving targeting therapy capacity.

Язык: Английский

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Tetrahedral framework nucleic acids/hyaluronic acid-methacrylic anhydride hybrid hydrogel with antimicrobial and anti-inflammatory properties for infected wound healing

International Journal of Oral Science, Год журнала: 2024, Номер 16(1)

Опубликована: Апрель 16, 2024

Abstract Bacterial resistance and excessive inflammation are common issues that hinder wound healing. Antimicrobial peptides (AMPs) offer a promising versatile antibacterial option compared to traditional antibiotics, with additional anti-inflammatory properties. However, the applications of AMPs limited by their antimicrobial effects stability against bacterial degradation. TFNAs regarded as drug delivery platform could enhance properties nanodrugs. Therefore, in this study, composite hydrogel (HAMA/t-GL13K) was prepared via photocross-linking method, which tFNAs carry GL13K. The injectable, biocompatible, be instantly photocured. It exhibited broad-spectrum inhibiting expression inflammatory factors scavenging ROS. Thereby, inhibited infection, shortened healing time skin defects infected full-thickness defect models reduced scarring. constructed HAMA/tFNA-AMPs hydrogels exhibit potential for clinical use treating microbial infections promoting

Язык: Английский

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Modulation of Cerebrospinal Fluid Dysregulation via a SPAK and OSR1 Targeted Framework Nucleic Acid in Hydrocephalus

Advanced Science, Год журнала: 2024, Номер 11(17)

Опубликована: Фев. 14, 2024

Abstract Hydrocephalus is one of the most common brain disorders and a life‐long incurable condition. An empirical “one‐size‐fits‐all” approach cerebrospinal fluid (CSF) shunting remains mainstay hydrocephalus treatment effective pharmacotherapy options are currently lacking. Macrophage‐mediated ChP inflammation CSF hypersecretion have recently been identified as significant discovery in pathogenesis hydrocephalus. In this study, pioneering DNA nano‐drug (TSOs) developed by modifying S2 ssDNA S4 with SPAK ASO OSR1 tetrahedral framework nucleic acids (tFNAs) synthesis via one‐pot annealing procedure. This construct can significantly knockdown expression OSR1, along their downstream ion channel proteins epithelial cells, thereby leading to decrease secretion. Moreover, these findings indicate that TSOs effectively inhibit M0 M1 phenotypic switch macrophages MAPK pathways, thus mitigating cytokine storm. vivo post‐hemorrhagic (PHH) models, reduce secretion rates, alleviate inflammation, prevent onset These compelling results highlight potential promising therapeutic option for managing hydrocephalus, applications future.

Язык: Английский

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A DNA tetrahedron-based nanosuit for efficient delivery of amifostine and multi-organ radioprotection

Bioactive Materials, Год журнала: 2024, Номер 39, С. 191 - 205

Опубликована: Май 21, 2024

Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages normal cells organs, leading serious physiological even life-threatening consequences. Amifostine (AMF) is a validated radioprotectant extensively applied in chemotherapy medicine, but the short half-life limits its bioavailability clinical applications, remaining as great challenge be addressed. DNA-assembled nanostructures especially tetrahedral framework nucleic acids (tFNAs) are promising nanocarriers with preeminent biosafety, low biotoxicity, high transport efficiency. The tFNAs also have relative long-term maintenance for structural stability excellent endocytosis capacity. We therefore synthesized tFNA-based delivery system of AMF multi-organ radioprotection (tFNAs@AMF, termed nanosuit). By establishing mice models accidental total body irradiation (TBI) radiotherapy model Lewis lung cancer, we demonstrated that nanosuit could shield from IR-induced DNA damage by regulating molecular biomarkers anti-apoptosis anti-oxidative stress. In model, pretreated exhibited satisfactory alteration superoxide dismutase (SOD) activities malondialdehyde (MDA) contents, functional recovery hematopoietic system, reducing pathological safeguarding lethal radiation. More importantly, showed selective organs without interferences tumor control cancer. Based on conveniently available tetrahedron-based nanocarrier, this work presents high-efficiency prolonged enhanced multi-organs. Such pioneers strategy translation potential radioactivity protection.

Язык: Английский

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Effects of Puerarin‐Loaded Tetrahedral Framework Nucleic Acids on Osteonecrosis of the Femoral Head

Small, Год журнала: 2023, Номер 19(41)

Опубликована: Июнь 14, 2023

Osteonecrosis of the femoral head (ONFH) is recognized as a common refractory orthopedic disease that causes severe pain and poor quality life in patients. Puerarin (Pue), natural isoflavone glycoside, can promote osteogenesis inhibit apoptosis bone mesenchymal stem cells (BMSCs), demonstrating its great potential treatment osteonecrosis. However, low aqueous solubility, fast degradation vivo, inadequate bioavailability, limit clinical application therapeutic efficacy. Tetrahedral framework nucleic acids (tFNAs) are promising novel DNA nanomaterials drug delivery. In this study, tFNAs Pue carriers used synthesized tFNA/Pue complex (TPC) exhibited better stability, biocompatibility, tissue utilization than free Pue. A dexamethasone (DEX)-treated BMSC model vitro methylprednisolone (MPS)-induced ONFH vivo also established, to explore regulatory effects TPC on BMSCs. This findings showed restore dysfunction attenuated induced by high-dose glucocorticoids (GCs) through hedgehog Akt/Bcl-2 pathways, contributing prevention GC-induced rats. Thus, for other osteogenesis-related diseases.

Язык: Английский

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Biomaterial‐based gene therapy

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Июнь 1, 2023

Gene therapy, a medical approach that involves the correction or replacement of defective and abnormal genes, plays an essential role in treatment complex refractory diseases, such as hereditary cancer, rheumatic immune diseases. Nucleic acids alone do not easily enter target cells due to their easy degradation vivo structure cell membranes. The introduction genes into biological is often dependent on gene delivery vectors, adenoviral which are commonly used therapy. However, traditional viral vectors have strong immunogenicity while also presenting potential infection risk. Recently, biomaterials attracted attention for use efficient vehicles, because they can avoid drawbacks associated with vectors. Biomaterials improve stability nucleic efficiency intracellular delivery. This review focused biomaterial-based systems therapy disease treatment. Herein, we recent developments modalities Additionally, discuss acid strategies, focus systems. Furthermore, current applications summarized.

Язык: Английский

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DNA tetrahedral nanostructures for the biomedical application and spatial orientation of biomolecules

Bioactive Materials, Год журнала: 2023, Номер 33, С. 279 - 310

Опубликована: Ноя. 24, 2023

DNA not only plays a vital role in nature as fundamental hereditary material for storing genetic material, but also serves well-defined functional example, building blocks the assembly of nanoscale bio-architectures by Watson-Crick base-pairing interaction. With development molecular biology, biotechnology and nanoscience, structural nanotechnology has achieved numerous advances, contributing to construction various nanostructures ranging from discrete objects one dimensional (1D), two (2D), three (3D) architectures. Among them, tetrahedral nanoarchitecture is intensively studied because simple 3D structure, easy design unique properties, such high rigidity, desirable biostability efficient cellular uptake without auxiliary species. This review summarizes research progress outlines applications biosensing, drug delivery targeted therapy. Moreover, dependence biological activity biomolecules on tetrahedron-mediated spatially-controlled arrangement great potential are discussed. In addition, challenges clinic tetrahedron-based platforms described, perspectives towards biomedical foreseen, our understandings further studies tetrahedron provided, aiming motivate interdisciplinary research.

Язык: Английский

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Tetrahedral Framework Nucleic Acids Based Small Interfering RNA Targeting Receptor for Advanced Glycation End Products for Diabetic Complications Treatment

ACS Nano, Год журнала: 2023, Номер 17(22), С. 22668 - 22683

Опубликована: Сен. 26, 2023

Complications arising from diabetes can threaten multiple organs. Advanced glycation end products (AGEs) play a significant role in inducing these complications. Highly processed diets and hyperglycemia facilitate the accumulation of AGEs body. Interaction between their main receptor (RAGE) initiates transmission intracellular inflammatory cell death signals, which ultimately lead to To counter AGEs-induced damage, we developed an siRNA-binding tetrahedral framework nucleic acids (TDN) system, termed Tsi, combines potent membrane penetrability serum stability TDN with gene-targeting specificity siRNA-RAGE. Tsi effectively persistently downregulates expression RAGE, thereby suppressing inflammation by blocking NF-κB pathway as well exhibiting antioxidant functions. Furthermore, regulates pyroptosis state macrophages via NLRP3/caspase-1 axis, inhibits spread signals maintains homeostasis. This is great significance for synergistic treatment strategy systemic complications patients refractory hyperglycemia. In summary, this study describes nanomedicine that targets RAGE suppresses AGE-induced inflammation. acid drug holds long-lasting efficacy independent lowering hyperglycemia, provides diabetic age-related diseases.

Язык: Английский

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