DNA dendrimer-based nanocarriers for targeted Co-delivery and controlled release of multiple chemotherapeutic drugs

RSC Advances, Год журнала: 2025, Номер 15(4), С. 2981 - 2987

Опубликована: Янв. 1, 2025

DNA-based nanomaterials have attracted increasing attention over the past decades due to their incomparable programmability and functionality. In particular, dendritic DNA nanostructures are ideal for constructing drug carriers highly branched structure. this study, an intelligent delivery system was constructed based on dendrimers, in which duplexes were utilized simultaneously loading both hydrophilic hydrophobic small molecule drugs. Additionally, cancer microenvironment-responsive cell-targeting moieties introduced into internal framework surface of nanostructures, respectively. Our research shows that these can enter cells through endocytosis disintegrate under reduction cellular glutathione, thereby achieving targeted co-delivery controlled release chemotherapeutic agents antisense oligonucleotides, providing effective strategy combined treatment tumors.

Язык: Английский

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Role of homonuclear B–B/N–N bonds in DNA nucleobases adsorption on boron nitride fullerenes: Biosensor and drug transport implications

Computational and Theoretical Chemistry, Год журнала: 2025, Номер unknown, С. 115188 - 115188

Опубликована: Март 1, 2025

Язык: Английский

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Photochemical regulatory strategies for nucleic acid function and their biomedical applications

Deleted Journal, Год журнала: 2024, Номер 2(3)

Опубликована: Июль 1, 2024

Abstract Nucleic acids are not only essential biomolecules that drive critical life processes such as growth, development, reproduction, inheritance, and mutation, but also serve significant markers for disease diagnosis, pathogen identification, cancer screening. Nevertheless, several challenges have hindered the widespread use of nucleic in biomedicine, susceptibility to degradation, limited cellular uptake efficiency, potential toxicity, uncontrollable activity. Photo‐regulation offers an effective solution address these challenges. It allows precise control acid structure function enhances stability safety their application biomedicine. In this review, we systematically review structural characteristics three primary photosensitive groups commonly used regulation molecules (i.e., photocleavable molecules, photoisomerization photo‐crosslinking molecules) under light irradiation. Subsequently, recent research advances development photo‐modulation strategies based on antisense oligonucleotides, RNA interference, amplification, CRISPR/Cas systems outlined. Finally, discuss faced photo‐regulatory outline future directions development.

Язык: Английский

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Insights into the formulation of lipid nanoparticles for the optimization of mRNA therapeutics

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Год журнала: 2024, Номер 16(5)

Опубликована: Сен. 1, 2024

Abstract mRNA‐based therapeutics increasingly demonstrate significant potential in treating various diseases, including infectious cancers, and genetic disorders. Effective delivery systems are crucial for advancing mRNA therapeutics. Lipid nanoparticles (LNPs) serve as an excellent carrier, widely validated their safety tolerability commercially available vaccines. Standard LNPs typically consist of four components: ionizable lipids (ILs), helper lipids, cholesterol, polyethylene glycol‐lipids (PEG‐lipids), with the structural design ILs gradually becoming a focal point research interest. The chemical structures formulations other components also significantly affect efficiency, targeting specificity, stability LNPs. complex may hinder clinical transformation have raised widespread concerns about safety. This review aims to summarize progress LNPs‐based trials, focusing on adverse effects that occurred during these trials. It discusses representative innovations LNP components, highlighting challenges ways this field. We firmly believe will promote further improvements designs compositions optimize article is categorized under: Nanotechnology Approaches Biology > Nanoscale Systems Biology‐Inspired Nanomaterials Lipid‐Based Structures

Язык: Английский

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miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 15, 2024

Abstract Background Spinal cord injury (SCI) is characterized by extensive demyelination and inflammatory responses. Facilitating the clearance of lipid droplets (LDs) within microglia contributes to creating a microenvironment that favors neural recovery provides essential materials for subsequent remyelination. Therefore, investigating MicroRNAs (miRNAs) regulate homeostasis after SCI elucidating their potential mechanisms in promoting LDs have become focal points research. Methods We established subacute C5 hemicontusion model mice performed transcriptomic sequencing on epicenter identify differentially expressed genes associated pathways. Confocal imaging was employed observe accumulation. Multi-omics analyses were conducted mRNA miRNA post-SCI. Pathway enrichment analysis protein-protein interaction network construction using bioinformatics methods, revealing miR-223- Abca1 as crucial miRNA-mRNA pair metabolism regulation. BV2 cell lines overexpressing miR-223 engineered, immunofluorescence staining, western blot, other techniques assess accumulation, relevant targets, factor expression, confirming its role regulating microglia. Results Histopathological results our confirmed aggregation at epicenter, predominantly Our during phase implicated ATP-binding cassette transporter A1 ( ) pivotal gene homeostasis, cholesterol efflux microglial activation. Integrative mRNA-miRNA multi-omics highlighted neuroinflammation process following SCI, potentially through regulation via . In vitro experiments cells demonstrated elevated levels enhance ABCA1 expression myelin debris LPS-induced cells. This promotes degradation clearance, induces shift toward an anti-inflammatory M2 phenotype. Conclusions summary, study unveils critical regulatory SCI. The mechanism which this occurs involves upregulation facilitates degradation, consequently alleviating burden, inhibiting polarization These findings suggest strategies target ABCA1, thereby augmenting may emerge appealing new clinical targets treatment.

Язык: Английский

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Recent Advances and Prospects of Nucleic Acid Therapeutics for Anti-Cancer Therapy

Molecules, Год журнала: 2024, Номер 29(19), С. 4737 - 4737

Опубликована: Окт. 7, 2024

Nucleic acid therapeutics are promising alternatives to conventional anti-cancer therapy, such as chemotherapy and radiation therapy. While therapies have limitations, high side effects, low specificity, drug resistance, nucleic work at the gene level eliminate cause of disease. treat diseases in various forms using different mechanisms, including plasmid DNA (pDNA), small interfering RNA (siRNA), anti-microRNA (anti-miR), microRNA mimics (miRNA mimic), messenger (mRNA), aptamer, catalytic (CNA), CRISPR cas9 guide (gRNA). In addition, acids many advantages nanomaterials, biocompatibility, design flexibility, immunogenicity, size, relatively price, easy functionalization. can a therapeutic effect by being used combination with nanostructures, inorganic nanoparticles, lipid nanoparticles (LNPs), etc. overcome physiological stability cell internalization efficiency. The field has advanced remarkably recent decades, more been approved, they already demonstrated their potential diseases, cancer. This review paper introduces current status advances therapy for treatment discusses tasks prospects ahead.

Язык: Английский

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Hierarchical DNA Octahedral Nanoplatform for in Situ Biosensing and Clinical Monitoring of Acute Lymphoblastic Leukemia

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Abstract Developing nanoscale platforms with high integration, assembly efficiency, and structural stability for performing complex computations in specific cells remains a significant challenge. To address this, the Three‐dimensional Hierarchical Octahedral Robotic (THOR) DNA nanoplatform is introduced, which integrates targeting, logic computation, sensing modules within single framework. This specifically binds to cancer cell surface proteins, releasing aptamer‐linked fuel chains initiate subsequent computational processes. Three gates efficiently compute any arbitrary binary combination of target proteins. The module employs catalytic hairpin detecting miRNAs sensitivity. THOR demonstrates robust functionality both vitro situ. As proof‐of‐concept, this distinguish acute lymphoblastic leukemia (ALL) patients from other subtypes healthy participants, achieving 100% accuracy applied. Additionally, approach reliably monitored therapeutic progress ALL patients, showing strong concordance bone marrow smear results. platform highlights feasibility constructing reliable, hierarchical, multifunctional analytical system based on polyhedron. It offers promising auxiliary tool clinical diagnostics monitoring.

Язык: Английский

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Lipid-siRNA Conjugates Targeting High PD-L1 Expression as Potential Novel Immune Checkpoint Inhibitors

Biomolecules, Год журнала: 2025, Номер 15(2), С. 293 - 293

Опубликована: Фев. 15, 2025

Programmed death 1 ligand (PD-L1), an important immune checkpoint molecule, is mainly expressed on cancer cells and has been shown to exert immunosuppressive effect T-cell function by binding programmed cell (PD-1) T-cells. Recently, inhibitors using antibody drugs such as nivolumab atezolizumab have attracted attention. However, clinical challenges, including limitations the scope of their application, are yet be addressed. In this study, we developed a novel inhibitor that targets PD-L1 lipid-siRNA conjugates (lipid-siPDL1s). The inhibitory lipid-siPDL1s expression was evaluated found strongly suppress mRNA expression. Notably, exerted significantly stronger than unmodified siPDL1. Interestingly, inhibited despite stimulation interferon-gamma, which induced overexpression genes. These results suggest could used inhibitors.

Язык: Английский

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Bone‐targeted hybrid extracellular vesicles for alveolar bone regeneration

Deleted Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Abstract Prolonged tooth loss causes a blade‐like narrowing of the alveolar bone, severely impairing chewing function and aesthetics complicating subsequent orthodontic or restorative treatments. Bone morphogenetic protein‐2 (BMP‐2) is widely used to induce osteogenesis; however, its lack cellular targeting in complex microenvironments often results significant side effects. Developing safe, stable, osteoblast‐targeted drug delivery system crucial for precise bone regeneration. Nanoparticles, as ideal vehicles, offer highly controllable targeting. This study introduces an innovative approach using DNA nanostructure‐modified BMP‐2‐loaded hybrid extracellular vesicles (EVs) formed by fusing liposomes EVs. Screening identified 180 nm optimal particle size EVs fusion efficiency. The achieved osteoblast‐specific attaching aptamer 19S membrane. were further combined with hydrogel sustained‐release system, creating platform that effectively repaired defects. demonstrated potential advancing tissue repair

Язык: Английский

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Hybrid-Designed Metal-Phenolic Nanoparticles for Synergistic Nano-Gene Periodontal Therapy

Biomaterials, Год журнала: 2025, Номер 322, С. 123417 - 123417

Опубликована: Май 17, 2025

Язык: Английский

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