ACS Sustainable Chemistry & Engineering
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2024
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IF 7.1
Yuhui Du,Xinqian Zheng,Yuan Ma,Fangjun Ge,Qiuyan Li,Hao Xiang,Xueyi Chen,Hai Zhou,Taolin Sun,Tingjian Chen
DNA-based biomaterials, including polyelectrolyte complex (PEC) hydrogels composed of DNA and other molecules, have received considerable attention due to their programmability and good biocompatibility. However, the cost for DNA synthesis is fairly high, especially for applications where a large quantity of DNA is needed. Construction of biomaterials using biomass-derived DNA is a feasible strategy to address this challenge. In this work, we fabricated and characterized PEC hydrogels with or without covalent cross-linking using biomass-derived DNA and chitosan (CS). Characterization results revealed detailed microstructures and mechanical properties of these two hydrogels, suggesting their potential application in DNA preservation and protein immobilization. We next developed a versatile DNA preservation strategy combining DNA-CS PEC hydrogel-based DNA encapsulation and chitosanase-mediated DNA release, which successfully maintained the integrity and functionality of various types of DNA, i.e., double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), plasmid DNA, and genomic DNA, during the treatment of DNase I and hydrogen peroxide (H2O2). Remarkably, this method also demonstrated good efficiency in protecting DNA containing a broadly used unnatural base pair, dNaM-dTPT3, against the attack of silver ion. Additionally, we developed a convenient and reliable strategy for protein immobilization with the covalently cross-linked PEC hydrogel. This strategy demonstrated good performance in the reusability of the immobilized enzyme, evidenced by 56.4% product yield of the initial cycle of usage achieved by the immobilized horseradish peroxidase (HRP) in the tenth cycle of usage. This work not only broadens the application scope of biomass-derived polymers, but also provides feasible strategies for the sustainable and cost-effective preservation and immobilization of biological macromolecules.
研究领域:
生物材料
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生物技术
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纳米技术
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生物化学
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分子生物学
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DOI
高影响因子
CANCER LETTERS
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2024
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IF 9.1
Ying Ning,Yu Chen,Tian Tian,Xinyan Gao,Xiaolan Liu,Jia Wang,Huijun Chu,Chenyang Zhao,Yufei Yang,Ke Lei,He Ren,Zhumei Cui
Neutrophil extracellular traps (NETs) have been shown to promote the metastatic potential of many kinds of tumors. Our study aimed to investigate the role and mechanisms of NETs in lymph node metastasis (LNM) of cervical cancer (CCa), and evaluated the therapeutic value of targeting NETs in CCa. Immunohistochemistry demonstrated that neutrophil infiltration and NETs formation were increased in CCa patients with LNM, as well as confirming a positive correlation between S100A7 expression and neutrophil infiltration in CCa. NETs enhanced the migratory capability of CCa by activating the P38-MAPK/ERK/NFκB pathway through interaction with TLR2. Digesting NETs with deoxyribonuclease 1 (DNase 1) or inhibiting TLR2 with chloroquine eliminated the NETs-induced metastatic potential of CCa. Additionally, NETs promoted lymphangiogenesis and increased the permeability of lymphatic vessels, thus facilitating translymphatic movement of CCa. CCa-derived S100A7 exhibited a chemotactic effect on neutrophils and promoted NETs generation by elevating ROS levels rather than activating autophagy in neutrophils. The mouse model with footpad implantation illustrated that DNase 1 effectively reduced LNM in LPS-induced mice and in mice seeded with S100A7-overexpressing CCa cells. In conclusion, our study reveals a new tumor-promoting mechanism of S100A7, clarifies the crucial role and mechanism of NETs in LNM of CCa, and indicates that the NETs-targeted therapy emerges as a promising anti-metastasis therapy in CCa.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
ANALYST
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2017
·Vol. 142
·期 15
·2796-2804
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IF 3.885
Zhenqiang Wang,Jixi Zhang,Feng Chen,Kaiyong Cai
The combination of fluorophore-labelled single-strand DNA probes and nanomaterial quenchers has shown great potential in miRNA detection. The development of advanced detection systems by understanding and controlling the fluorescence quenching/recovery via nanoquenchers’ microstructures and local morphologies is an attractive area warranting further investigations. Inspired by nanopore sequencing, we present a novel miRNA sensing strategy using fluorophore-labeled DNA as probes and a type of large-pore-sized mesoporous polydopamine nanoparticles (MPDA-L, 70 nm in diameter) as fluorescence quenchers. It is revealed that the quenching efficiency of MPDA-L towards the fluorophore labelled on the probe, reached more than 99% at a relatively low particle concentration. Moreover, the mesopores effectively protected the probe DNA from cleavage by DNase I which was used for signal amplification. Sensitive detection of miRNA with a low detection limit of 32–40 pM, as well as a linear detection range of up to 5 nM, was realized by the mesopore effects via a greatly improved differential affinity of ssDNA and the probe–miRNA heteroduplex toward the surface of nanoquenchers. Interestingly, enhanced DLVO (Derjaguin–Landau–Verwey–Overbeek) repulsion generated inside the pore surface by the negative surface–curvature effect correlates with the improved duplex detachment and fluorescence recovery. The developed strategy can be successfully applied to quantify down-regulated let-7a and up-regulated miRNA-21 in different types of cancer cells by using total RNA samples from cell lysate. These findings are expected to inspire strategies and pave a way for utilizing porous nanomaterials for constructing miRNA detection systems.
研究领域:
纳米技术
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生物医学工程
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Science Bulletin
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2025
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IF 21.1
Fangke Zhang,Jiancheng Zheng,Fei Wang,Yaping Zhuang,Yunkai Tang,Juan Wang,Yawei Du,Wei-Li Zhao,Min Lu,Weiguo Hu,Wenguo Cui
Mutations in cytoplasmic DNA-degrading enzymes can lead to the accumulation of cytoplasmic DNA (cytoDNA), which excessively activates DNA-sensing pathways and exacerbates inflammatory aging. Reducing cytoDNA levels to suppress DNA-sensing mechanisms is therefore critical for treating elderly-onset rheumatoid arthritis (EORA). In this study, we constructed Trex1 mRNA loaded lipid nanoparticles (LNPs) via microfluidics and prepared DNase I loaded polydopamine (PDA) nanoparticles through oxidative polymerization. These two components were co-encapsulated into methacrylated hyaluronic acid (HAMA) microspheres using microfluidic photopolymerization. The LNPs incorporate cationic lipids to facilitate mRNA loading and promote endosomal escape, enabling efficient translation of TREX1 and subsequent recognition and degradation of cytoDNA. Meanwhile, cationic mesoporous polydopamine electrostatically adsorbs and degrades extracellular DNA. The microspheres function as a reservoir for sustained nanoparticle release, enabling synergistic inhibition of DNA sensing pathways. This microsphere based vaccine upregulates TREX1 expression in antigen-presenting cells (APCs) and reduces cytoDNA levels, thereby suppressing overactivation of the cGAS-STING signaling axis and promoting immune tolerance. It also attenuates the differentiation of CD4+ T cells into Th1, Th2, Th17, and Treg subsets. In an aged rat model of rheumatoid arthritis, the vaccine alleviated soft tissue swelling, synovitis, and cartilage and bone damage. By clearing excess cytoDNA and restraining DNA-sensing hyperactivation, this vaccine induces cellular immune tolerance and represents a promising therapeutic strategy for rheumatoid arthritis in the elderly.
研究领域:
免疫学
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纳米医学
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分子生物学
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疫苗学
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风湿病学
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衰老研究
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基因治疗
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yi Lu,Yibo Shan,Jianwei Zhu,Zhiming Shen,Wenxuan Chen,Hao Chen,Hongcan Shi
Patch tracheoplasty offers an alternative approach to repairing congenital tracheal stenosis without tension but poses a higher risk of restenosis, granulation tissue formation, and tracheal collapse. The use of tissue-engineered patches for tracheoplasty has been proposed as a solution. Studies suggest that decellularization methods are effective in preparing tracheal patches; however, further research is necessary to improve their efficiency and safety. This study introduces a novel decellularization method using 3-[(3Cholamidopropyl)dimethylammonio]propanesulfonate (CHAPS) and DNase to create a biocompatible tracheal matrix. To enhance the regeneration of epithelial regions within decellularized tracheal scaffolds, this study conducted experimental validations at various levels, both in vivo and in vitro, by introducing extracellular vesicles derived from adipose mesenchymal stem cells as an intervention measure. The ability to promote epithelial regeneration was validated both in vitro and in vivo by incorporating a GelMA hydrogel loaded with adipose-derived mesenchymal stem cell extracellular vesicles (ADMSC-EVs). Evaluation of HBE cell proliferation on tracheal patches treated with varying concentrations of ADMSC-EVs, along with migration and invasion experiments on ADMSC-EV-treated HBE cells, demonstrated enhanced epithelialization in vitro. The inflammatory response and vascular regeneration were assessed via subcutaneous implantation in rats for two weeks. In a rabbit tracheal defect model, the hydrogel loaded with ADMSC-EVs accelerated re-epithelialization in the patch area. This approach shows promise as a novel material for tracheal patching in clinical applications.
研究领域:
组织工程
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再生医学
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干细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
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