Journal of Materials Chemistry B
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2024
·Vol. 12
·期 26
·6442-6451
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IF 6.1
Jia-Hao Bai,Qing-Tao Yu,Yi-Wu Wang,Chun-Fa Chen,Lian-Ju Ma,Yue Yuan,Yong-Jun Gan,Jia-Qi Yang,Shu Zhu,Yu-Hang Ran,Li-Lei Zhang,Hang Qian,Zheng-Huan Zhao,Qian Liu
Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.
研究领域:
纳米医学
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癌症治疗
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分子生物学
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Chunfa Chen,Quan Li,Beinuo Wang,Qian Liu,Zi Wang,Bihang Zhang,Lu Wang,Yujuan Zou,Ziye Mou,Chengshan Ren,Zaichun You,Bin Wang,Zhi Xu,Hang Qian
Acute lung injury (ALI) is characterized by widespread inflammation and oxidative stress, leading to impaired gas exchange and significant morbidity. In this study, we propose a potential approach using a magnesium-free DNA self-assembly strategy to assemble a DNA nanotube that carries agmatine and microRNA-126b mimics (NT AGM -126). Agmatine not only reduces electrostatic repulsion between DNA helices, thereby facilitating the folding of the DNA nanotube, but also serves as a drug that inhibits iNOS signaling. The microRNA-126b mimics restore the downregulated microRNA-126b in macrophages and suppress inflammation by targeting high mobility group box 1 (HMGB1). Preliminary results indicated that agmatine can effectively facilitate the assembly of the DNA nanotube, improve serum stability, and enhance the cellular uptake efficiency of NT AGM -126. Further in vitro and in vivo results demonstrate that NT AGM -126 effectively reduces oxidative stress and inflammation by downregulating iNOS and HMGB1, providing a combined therapeutic effect in ALI. This study highlights the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform for treating inflammatory diseases, broadening the application of DNA nanotechnology in biomedical research. Statement of Significance This study introduces a promising therapeutic approach using a magnesium-free DNA self-assembly strategy to create a DNA nanotube (NT AGM -126) that carries agmatine and microRNA-126b mimics. The agmatine not only aids in the assembly and stability of the DNA nanotube but also inhibits iNOS signaling, while the microRNA-126b mimics restore downregulated microRNA-126b in macrophages and suppress inflammation by targeting HMGB1. Preliminary and further results demonstrate that NT AGM -126 effectively reduces oxidative stress and inflammation, providing a synergistic therapeutic effect in ALI. This study underscores the potential of agmatine-facilitated DNA nanostructures as a versatile drug delivery platform, broadening the application of DNA nanotechnology in the treatment of inflammatory diseases and advancing biomedical research.
研究领域:
生物医学工程
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Run Chen,Pengchao Sun,Xiao Chu,Xiaorong Pu,Yang Yang,Nan Zhang,Yongxing Zhao
Background Aptamers have been widely used as targeted therapeutic agents due to its relatively small physical size, flexible structure, high specificity, and selectivity. Aptamers functionalized nanomaterials, not only enhance the targeting of nanomaterials, but can also improve the stability of the aptamers. We developed aptamer C2NP (Apt) conjugated straight DNA nanotubes (S-DNT-Apt) and twisted DNA nanotubes (T-DNT-Apt) as nanocarriers for doxorubicin (DOX).Methods The twisted DNA nanotubes (T-DNT) and straight DNA nanotubes (S-DNT) were assembled with a scaffold and hundreds of staples. Apt was site-specifically anchored on DNA nanotubes with either different spatial distribution (3 or 6 nm) or varied stoichiometry (15Apt or 30Apt). The developed nanocarriers were characterized with agarose gel electrophoresis and transmission electron microscopy. The drug loading and release in vitro were evaluated by measuring the fluorescence intensity of DOX using a microplate reader. The stability of DNT in cell culture medium plus 10% of FBS was evaluated by agarose gel electrophoresis. The cytotoxicity of DNA nanostructures against K299 cells was tested with a standard CCK8 method. Cellular uptake, cell apoptosis, cell cycle and reactive oxygen species level were investigated by flow cytometry. The expression of p53 was examined by Western Blot.Results T-DNT-30Apt-6 exhibited the highest cytotoxicity when the concentration of Apt was 120 nM. After intercalation of DOX, the cytotoxicity of DOX@T-DNT-30Apt-6 was further enhanced due to the combination of chemotherapy of DOX and biotherapy of Apt. The enhanced cytotoxicity of DOX@T-DNT-30Apt-6 can be explained by the increase in the cellular uptake, cell apoptosis and intracellular ROS levels. Additionally, the interaction between Apt and its receptor CD30 could upregulate the expression of p53.Conclusion These results demonstrate that both stoichiometry and spatial arrangement of Apt on T-DNT-Apt influence the anticancer activity. The developed twisted DNA nanotubes may be a solution for the synergistic treatment of cancer.
研究领域:
纳米技术
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生物医学工程
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药学
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癌症研究
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nano Today
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2024
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IF 13.2
Nier Wu,Shengnan Fu,Chenxi Dai,Lingfei Hu,Jiaxin Li,Fangzhou Chen,Lin Wang,Xin Su,Dongsheng Zhou
Antimicrobial peptides (AMPs) represent a good alternative for treating infections to overcome increasing antibiotic resistance problems. DNA nanostructures have been utilized as the delivery carrier of AMPs to enhance their performance, but mechanisms of action remain largely unclear. In this work, DNA nanotube (DNT) was chosen as a preferred carrier of AMPs owing to its high binding affinity and loading capacity, and an engineered broad-spectrum AMP named RP557 was screened as the cargo though molecular simulation and subsequent loading experiments. RP557 molecules were then loaded onto DNT through electrostatic interaction to construct RP557@DNT nanocomplex for improved anti-infective therapy. Loaded RP557 possessed the lower cytotoxicity to fibroblasts and epithelial cells and the higher compatibility to red blood cells relative to free RP557 in vitro , and RP557@DNT displayed the highly favored biodegradability and biosafety at the animal level. In addition, compared to free RP557, RP557@DNT endowed better bactericidal activity in vitro and in vivo because loaded RP557 exhibited higher resistance to serum protease degradation and controlled release onto bacterial cell membrane. The high therapeutic effect of RP557@DNT primarily depended on the acceleration of inflammation resolution (involving the reduction in proinflammatory factor production, innate immune cell recruitment, and adaptive immunity) and tissue repair (involving the up-regulation of multiple epidermal and dermal repair pathways). In summary, RP557@DNT showed significantly enhanced anti-enzymolysis, antibacterial activity, and biosafety relative to free RP557, and thus it represented a high-efficiency antibiotics-alternative strategy for treating refractory infections.
研究领域:
纳米技术
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药学
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微生物学
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免疫学
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产品关联
DOI
高影响因子
Science China-Life Sciences
·
2024
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IF 8
Zheng Cheng,Song Lanlan,Yu Chang,Zhu Lingye,Zhang Jing,Wang Ning,Liu Mengchu,Li Shini,Wang Liangxing,Shen Zhifa,Huang Xiaoying
Chemotherapy is regarded as a widely used and effective treatment strategy for lung cancer, although most conventional chemotherapeutics cause severe toxic side-effects due to their indiscriminate attacks on both cancerous and normal cells. Although nucleic acid nanomaterials are emerging as a promising drug delivery strategy, their clinical applications are limited by rapid degradation by nucleases and difficulties in targeting cancer cells. In this study, we have developed a Rhein-loaded aptamer-based DNA nanotube (DNT-S6@Rhein) for the targeted and efficient therapy of non-small cell lung cancer. Through the palindrome segments, two specified oligonucleotides were hybridized and folded into the well-defined nanotubes (DNT-S6), with the S6 aptamer distributed outside. The obtained nanotubes exhibited excellent serum stability and targeting ability towards A549 cells due to the firm structure and decoration of the S6 aptamer. Rhein, as an antitumor drug and DNA intercalator, can be effectively inserted into the DNT-S6. The drug-loaded nanotubes rapidly disassembled in intracellular environment and then the released Rhein was found to activate cellular apoptotic process and significantly suppress proliferation, migration and invasion of A549 cells. Moreover, DNT-S6@Rhein could efficiently accumulate in tumor regions, offering compelling therapeutic efficacy and biocompatibility under both in vitro and in vivo settings. These findings of this study provide a promising strategy for mitigating the inevitable systemic side-effects of chemotherapy and expand the potential application of DNA nanostructure on targeted drug delivery.
研究领域:
癌症研究
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纳米技术
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药物递送系统
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分子生物学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）