Self-Assembled Multivalent Aptamer Drug Conjugates: Enhanced Targeting and Cytotoxicity for HER2-Positive Gastric Cancer DOI

Wenjuan Ma,

Yuting Yang, Zhiqiang Liu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(37), P. 43359 - 43373

Published: Sept. 6, 2023

Antibody drug conjugates (ADCs) have shown promise to be the mainstream chemotherapeutics for advanced HER2-positive cancers, yet issues of poor delivery efficiency, limited chemotherapeutic effects, severe immune responses, and resistance remain addressed before clinical applications ADCs. The DNA aptamer-guided (ApDCs) are receiving growing attention specific tumors due their excellent tumor affinity low cost. Therefore, developing a multivalent ApDC nanomedicine by combining anti-HER2 aptamer (HApt), tetrahedral framework nucleic acid (tFNA), deruxtecan (Dxd) together form HApt-tFNA@Dxd might help address these concerns. In this study, HER2-targeted modified tetrahedron (HApt-tFNA) was employed as system delivery, adoption tFNA could effectively enlarge drug-loading rate compared ApDCs previously reported. Compared with free Dxd tFNA@Dxd, showed better structural stability, targeted cytotoxicity gastric cancer, increased tissue aggregation ability in tumors. These features superiorities make promising medicine Our work developed new targeting nanomaterials agents, which represents critical advance toward novel DNA-based promoting potential cancer therapy.

Language: Английский

A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis DOI Creative Commons
Yong Li, Zhengwen Cai, Wenjuan Ma

et al.

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 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.

Language: Английский

Citations

74

DNA framework signal amplification platform-based high-throughput systemic immune monitoring DOI Creative Commons
Ye Chen, Xingyu Chen, Bowen Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 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.

Language: Английский

Citations

49

Framework Nucleic Acids‐Based VEGF Signaling Activating System for Angiogenesis: A Dual Stimulation Strategy DOI Creative Commons
Yichen Ge, Qingxuan Wang,

Yangxue Yao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(21)

Published: March 9, 2024

Abstract Angiogenesis is crucial for tissue engineering, wound healing, and regenerative medicine. Nanomaterials constructed based on specific goals can be employed to activate endogenous growth factor‐related signaling. In this study, the conventional single‐stranded DNA self‐assembly into tetrahedral framework nucleic acids (tFNAs), Apt02 acid aptamer dimethyloxallyl glycine (DMOG) small molecule are integrated a complex via template‐based click chemistry reaction toehold‐mediated strand displacement reaction. Thus, being able simulate VEGF (vascular endothelial factor) function stabilize HIF (hypoxia‐inducible factor), functional whole applied angiogenesis. Cellular studies demonstrate that tFNAs‐Apt02 (TAC) has conspicuous affinity human umbilical vein cells (HUVECs). Further incubation with DMOG yields tFNAs‐Apt02‐DMOG (TACD), which promotes secretion, in vitro blood vessel formation, sprouting, migration of HUVECs. Additionally, TACD enhances angiogenesis by upregulating VEGF/VEGFR signaling pathways. Moreover, diabetic mouse skin defect repair process, increases formation collagen deposition, therefore accelerating healing. The novel strategy simulating stabilizing blood‐vessel vivo potential broad applications vascularization field.

Language: Английский

Citations

37

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

Qi Cai,

Qiang Sun, Dexuan Xiao

et al.

International Journal of Oral Science, Journal Year: 2024, Volume and Issue: 16(1)

Published: April 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

Language: Английский

Citations

36

Synergistic Osteogenic and Antiapoptotic Framework Nucleic Acid Complexes Prevent Diabetic Osteoporosis DOI
Long Bai,

Maogeng Feng,

Qiuwen Zhang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(28)

Published: March 12, 2024

Abstract Diabetes mellitus (DM) is characterized by elevated blood glucose and advanced glycation end product (AGEs) levels. Increased AGEs in bone tissue inhibit osteogenic differentiation marrow mesenchymal stem cells (BMSCs), leading to loss osteoporosis diabetic patients. Enhancing the capacity of BMSCs presence abundant can improve health prevent DM The flavonoid, Quercetin, has anti‐inflammatory, antibacterial, antitumor properties; however, it insoluble water thus not easily absorbed body. Nanodrug delivery systems such as tetrahedral framework nucleic acids (tFNAs) exhibit excellent biocompatibility, efficient cell uptake, drug piggybacking. In present study, tFNAs with quercetin complexed form a novel nanodrug (tFNAs/Que) that combined features both components. tFNAs/Que promote an vitro AGEs‐rich environment, maintain mass, mice vivo. mechanism against may be related JNK signaling pathway. conclusion, shown dual regulatory role promoting inhibiting apoptosis. Such feature promising for prevention treatment osteoporosis.

Language: Английский

Citations

31

Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control DOI

Xingyu Long,

Min Liu,

Yayun Nan

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Jan. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Language: Английский

Citations

29

A DNA tetrahedron-based nanosuit for efficient delivery of amifostine and multi-organ radioprotection DOI Creative Commons
Yuting Yang, Yang Jl, Jianwei Zhu

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 39, P. 191 - 205

Published: May 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.

Language: Английский

Citations

21

DNA-Based Nanostructured Platforms as Drug Delivery Systems DOI Creative Commons
Manish Kumar, Abhishek Jha, Brahmeshwar Mishra

et al.

Chem & Bio Engineering, Journal Year: 2024, Volume and Issue: 1(3), P. 179 - 198

Published: Jan. 9, 2024

DNA nanotechnology has recently provided a novel approach for developing safe, biocompatible, biodegradable, non-immunogenic, and non-toxic drug delivery systems. nanostructures have numerous advantages deployment as platforms, owing to programmable assembly, ease of production, reproducibility, precise control over size, shape, function. can dramatically improve the poorly soluble drugs, decreasing cytotoxicity normal tissues improving therapeutic effectiveness. Using different conjugation methods, be precisely integrated with wide range functional moieties, including proteins, peptides, aptamers, polymers, lipids, inorganic nanoparticles, targeting groups, enhance nanostructure stability, extend circulation, specify delivery. Smart ligands or stimuli-responsive moiety target, minimize loss attributable prior release off-target distribution, target accumulation, promote cellular internalization, bypass efflux pumps, avoid adverse effects. Target-specific by smart nanostructures, in turn, maximizes concentration, reaching locations at faster rate preventing failure while also lowering dose needed effect. This Review provides an overview encapsulation selective desired sites. are platform improved performance that may used treat variety diseases.

Language: Английский

Citations

17

Development of an Inhalable DNA Tetrahedron MicroRNA Sponge DOI
Lan Yao, Geru Zhang, Yun Wang

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Abstract In designing aerosolized drugs, the challenge lies in achieving optimal penetration and retention. Existing delivery systems prioritize larger particles for prolonged intrapulmonary retention, compromising speed. Conversely, smaller nanoparticles face rapid clearance limited RNA sponges featuring multiple microRNA binding sites exhibit promising potential gene expression regulation. However, complex structure of frequently utilized cyclic sponge impedes cellular uptake, restricting its application. This study proposes an innovative approach using a compact tetrahedral framework nucleic acid to construct inhalable sponge. Distinguished by simplified structure, this ensures effective inhibition, tissue penetration, residency through prompt endocytosis. Validated acute lung inflammation models, demonstrates swift restoration local immune homeostasis. design addresses critical need aerosol vehicles that balance efficient sustained offering solution

Language: Английский

Citations

16

A DNA-based nanorobot for targeting, hitchhiking, and regulating neutrophils to enhance sepsis therapy DOI
Mi Zhou,

Yifei Lu,

Yuanlin Tang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 318, P. 123183 - 123183

Published: Feb. 10, 2025

Language: Английский

Citations

2