Cancer Medicine
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2024
·Vol. 13
·期 17
·e70197
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IF 2.9
Yidan Ma,Yifei Wang,Lei He,Jun Du,Lin Li,Zhixin Bie,Yuanming Li,Xiaomao Xu,Wei Zhou,Xiaonan Wu,Li Yang,Jing Di,Chenyang Li,Xiaoguang Li,Dongge Liu,Zheng Wang
Backgroud Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell-free DNA (cfDNA) in patients with non-small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell-free RNA (cfRNA) is critical for resolving the issue. Methods A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi-gene mutations detection by RT-qPCR. Results Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4-ALK, ROS1, RET fusions, and MET ex14 skipping. Conclusion These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.
研究领域:
医学
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分子生物学
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DOI
高影响因子
Cancers
·
2021
·Vol. 13
·期 4
·664
·
IF 6.639
Li-Yue Sun,Zi-Ming Du,Yu-Ying Liu,Yan-Hong Li,Xiao-Min Liu,Ting Wang,Jian-Yong Shao
Simple SummaryPrevious studies have established an electrochemical detection method for the rapid detection of cfDNA (circulating free DNA) methylation and found that this technology might be a potential method for cancer diagnosis. However, the underlying mechanism and its role in the diagnosis and prognosis of malignant tumors are not well-characterized. In present study, we utilized the electrochemical detection method to detect the DNA methylation status by using electron microscopies and infrared spectroscopy and found that DNA with different methylated levels adsorbed to the gold surface differently, which was likely mediated by hydrophobic bonds. In addition, after detection of the cfDNA methylation status from 505 normal individuals, 725 cancer patients before treatment, and 549 patients after treatment, we found that the cfDNA adsorption rate could be used as an indicator for the diagnosis and prognosis prediction of pan-cancer. Our research provides a novel method for the liquid biopsy of cancer for diagnosis and prognosis predictions.AbstractPrior research has established an electrochemical method based on the differential adsorption capacity of gold surfaces with different methylated DNA degrees and found that this method might be valuable for cancer diagnosis by detecting circulating free DNA methylation. However, further investigation on the underlying mechanism and validation of its diagnostic and prognostic values in a large cohort of malignant tumors was limited. We found that DNA with different methylation levels formed particles of diverse sizes on the gold surface. Hydrophobic bonds played a significant role in the binding process of methylated DNA to the gold surface. The detection condition of an adsorption time of 10 min and temperature of 20 °C was optimal. In a large cohort of plasma samples from the patients with different malignant tumors, as well as normal individuals, we found that the electrochemical detection method based on the differential adsorption capacity of methylated DNA degree on a gold surface could be used as a noninvasive tool for malignant tumor diagnosis and prognostic evaluation. The diagnostic efficiency of this method in malignant tumors was even slightly better than that of the current tumor biomarkers widely used in routine clinical practice (circulating free DNA (cfDNA) vs. carcinoembryonic antigen (CEA), 0.8131 vs. 0.7191 and cfDNA vs. CA19-9, 0.7687 vs. 0.6693).Keywords:electrochemical;circulating free DNA methylation;malignant tumor;diagnostic;prognostic
研究领域:
医学
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分子生物学
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肿瘤学
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PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Lulu Liu,Chenxin Lu,Zhenchao Tao,Zhengbao Zha,Hua Wang,Zhaohua Miao
Polydopamine nanomaterials have emerged as one of the most popular organic materials for management of oxidative stress-mediated inflammatory diseases. However, their current anti-inflammatory ability is still unsatisfied because of limited phenolic hydroxyl groups and oxidation reaction-medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, we reported two-dimension (2D) cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti-inflammatory capability. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibited 3∼4-fold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti-inflammatory ability, polylysine molecules were absorbed on the surface of PDA NSs to endow the scavenging capability of cell-free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms revealed that cationic PDA NSs could concurrently activate Keap1-Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual-scavenging capability effectively alleviated the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5-aminosalicylic acid. This article is protected by copyright. All rights reserved
研究领域:
材料科学
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纳米技术
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药学
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炎症研究
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DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Wenjie Xi,Weijie Wu,Lili Zhou,Qi Zhang,Shushu Yang,Lihong Huang,Yijun Lu,Jing Wang,Xinjin Chi,Yang Kang
Sepsis is a serious and life-threatening condition, which can lead to organ failure and death clinically. Abnormally increased cell-free DNA (cfDNA) and inflammatory cytokines are involved in the development and progression of sepsis. Thus, cfDNA clearance and down-regulation of inflammatory factors are essential for the effective treatment of sepsis. Here we designed and constructed a polydopamine-based multifunctional nanoparticle for the treatment of sepsis. These nanoparticles (NPs) are composed of polydopamine (PDA) grafted with cationic polyethyleneimine (PEI). On the one hand, the NPs can utilize the electrostatic interaction to effectively adsorb cfDNA in blood, then effectively inhibiting the activation of toll like receptors (TLRs) and nuclear factor kappa B (NF-κB) pathways induced by cfDNA. On the other hand, the NPs have an immunomodulatory function, which can effectively convert pro-inflammatory macrophage (M1) into anti-inflammatory macrophage (M2), thus reduce the release of inflammatory cytokines and slow down the inflammatory storm of sepsis. In addition, the NPs possess good reactive oxygen species (ROS) scavenging ability. Briefly, the effective treatment of sepsis can be achieved by multiple strategies of effectively capturing the inflammatory triggering factor cfDNA, modulating the polarization of M1 macrophage to M2 macrophage and scavenging ROS, which has a promising clinical application.
研究领域:
医学
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免疫学
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纳米医学
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感染与炎症
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DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
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2025
·
IF 4.6
Xin Bao,Guang Xin,Qilong Zhou,Tao Wang,Xinrui Xu,Lijuan Feng,Chengyu Wan,Fangyuan Jing,Yijiang Liu,Yangbo Liu,Xiaoting Chen,Wen Huang
Acute pancreatitis (AP) is a common inflammatory disease that seriously threatens people's lives and health. Excessive reactive oxygen species (ROS) and cell-free DNA (cfDNA) are significant contributors to the advancement of AP. In this study, a nanoparticle with a dual function to clear ROS and cfDNA was developed for the treatment of acute pancreatitis. Cationic polyethyleneimine (PEI) was used to modify Mn 3 O 4 , resulting in the creation of Mn 3 O 4 -PEI nanoparticles, which exhibited strong binding to cfDNA and the ability to scavenge ROS. In vitro, Mn 3 O 4 -PEI showed significant inhibition of ROS and cfDNA-induced inflammation and demonstrated therapeutic effects in a model of acute pancreatitis induced by sodium taurocholate (STC). This research introduces a new nanomedicine approach for the treatment of AP.
研究领域:
纳米医学
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炎症性疾病
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活性氧清除
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细胞游离DNA靶向
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药物递送
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DOI
PubMed
高影响因子
RSC Advances
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2019
·Vol. 9
·期 6
·3407-3415
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IF 3.049
Xinglu Jiang,Chenggui Zhao,Xiaobo Fan,Wei Xu,Rui Zhang,Hongbo Xu,Guoqiu Wu
Cell-free DNA (cfDNA) in blood, which stems from the fetus of pregnant women and tumor in cancer patients, has gained attention in molecular diagnosis. However, cfDNA is less stable, and its amount in the serum is extremely low; these are critical barriers for the utilization of this resource. In this study, a DNA-modified polyacrylamide hydrogel (DNA-Gel) was prepared, and a specialized device was designed to simultaneously catch, purify, concentrate, and detect targeted cfDNA by electrophoresis. We demonstrated that 20–1000 bp ssDNA and dsDNA could be caught and released by the DNA-Gel-based device with high specificity and sensitivity. Upon increasing the number of cycles and electrophoresis time, higher DNA purity and density were achieved, and the separation of serum proteins, untargeted cfDNA, and other charged molecules was promoted. As low as 10 pg μL−1 of DNA could be detected using the DNA-Gel after four cycles of concentration. We also detected 1 fg μL−1 of DNA in the serum with 16 cycles of concentration, followed by 25 PCR cycles. We also designed a device to obtain DNA from the DNA-Gel. We found that the DNA loss rate was around 50%, and A260/A280 was close to 1.7. Thus, we have designed a cost-effective and highly economical device to purify DNA at low concentrations with high specificity and selectivity.
研究领域:
分子生物学
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生物医学工程
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分析化学
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遗传学
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2025
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IF 26.8
Haiying Liang,Jiamiao Jiang,Jiajun Miao,Jia Sun,Hanfeng Qin,Xiaoting Zhang,Lishan Zhang,Hao Tian,Yicheng Ye,Junbin Gao,Fei Wang,Shuai Han,Fei Peng,Yingfeng Tu
Overproduction of pathogenic cell-free DNA (cfDNA) and reactive oxygen species (ROS) plays crucial roles in the onset and perpetuation of ulcerative colitis (UC). Inspired by sweeping robots, a magnesium@polylactic acid-glycolic acid copolymer@polyethylenimine (Mg@PLGA@PEI) microswimmer capable of cleaning off deleterious disease triggers along its path of progress is designed. Mg@PLGA@PEI is successfully synthesized by adopting a core-shell structure with a small opening which allows for Mg-water reaction. The distinctive motility performance resulting from sustained detachment of the produced hydrogen not only contributes to strengthened hydrogen diffusion concomitant with potentiated ROS neutralization, but also facilitates the contacting probability with microenvironmental cfDNA and thus enhances the DNA binding efficiency. By integrating these merits, the developed Mg@PLGA@PEI confers desirable curative efficacy in a classical DSS-induced acute colitis mouse model. Enema administration of Mg@PLGA@PEI microswimmers substantially alleviates the manifestations related to UC, as evidenced by the body weight recovery, colon length retention, colon tissue protection, and attenuated intestinal inflammation, which is attributed to the active scavenging of cfDNA and ROS. This work provides a paradigm for a drug-free strategy competent in spontaneously eliminating causative triggers with minimal side effects, which presents a promising alternative for the active therapy of UC or other cfDNA- and ROS-related diseases in the clinic.
研究领域:
生物医学工程
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材料科学
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消化系统疾病
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Xie Hanbin,Wei Cong,Xiong Chang,Huang Ziyan,Chen Chaojin,Xiao Xue,Zhang Linan,Lin Zhenjia,Yao Weifeng,Zhao Tianyu,Hei Ziqing
Intestinal ischemia/reperfusion (I/R) injury is a common life-threatening condition. Inflammatory dysregulation plays a crucial role in the pathological progression of intestinal I/R injury, indicating that controlling excessive inflammatory responses can be an effective strategy for mitigating I/R injury. Herein, after establishing a correlation between cell-free DNA (cfDNA) levels and postoperative inflammatory factors in samples from patients with intestinal I/R, we tested a cfDNA-scavenging approach for the treatment of intestinal I/R injury. Poly-ε-caprolactone (PCL) microspheres (Micro DEA2k) functionalized with a pH-responsive cationic polymer (DEA2k) to efficiently scavenge cfDNA were synthesized and evaluated.These microspheres exhibited enhanced cfDNA adsorption under inflammation-induced acidic conditions, along with low toxicity, reduced non-specific protein binding, and extended peritoneal retention. In a mouse model of intestinal I/R injury, the intraperitoneal injection Micro DEA2k effectively bound cfDNA, regulated the mononuclear phagocytic system, decreased the number of M1 macrophages, suppressed inflammation, and significantly improved the survival rate of the mice. These findings suggest that cfDNA scavenging using cationic microspheres has considerable potential for alleviating intestinal I/R injury. Graphical
研究领域:
药理学
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免疫学
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材料科学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yang Zhou,Zhiyong Liu,Mengyuan Yin,Chenglong Ge,Zhongmin Liu,Renxiang Zhou,Duanmin Hu,Lichen Yin
In autoimmune diseases (AIDs), the interplay of various inflammatory mediators, including cell-free DNA (cfDNA), reactive oxygen species (ROS), and pro-inflammatory cytokines, contributes to a self-amplified inflammatory cascade that greatly limits the efficacy of existing single-target therapies. Herein, biomimetic nanoparticles (NPs) with reversible macrophage membrane (RM) cloaking are developed to scavenge multiple inflammatory mediators for the multifaceted immunomodulation against AIDs. The NPs are constructed by adsorbing catalase (CAT) onto the cationic, spherical polypeptide (GP), followed by surface coating with RM. Because of the RM coating, the NPs feature long blood circulation and efficient inflammation homing after systemic administration. In the inflamed tissues, RM neutralizes multiple pro-inflammatory cytokines and CAT decomposes H 2 O 2 to alleviate the oxidative stress. Meanwhile, the O 2 bubbles generated from H 2 O 2 decomposition propels shedding of RM, thus exposing inner GP to mediate robust cfDNA scavenging. Consequently, the NPs effectively alleviate inflammation and facilitate tissue repair in mouse models of AIDs including rheumatoid arthritis and inflammatory bowel disease. This study reports a bio-inspired strategy for the multi-target interruption of the self-amplified inflammatory cascade, and renders promising implications for the clinical management of AIDs.
研究领域:
免疫学
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纳米医学
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炎症生物学
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自身免疫病
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生物材料
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转化医学
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药物递送
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DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-15
·
IF 14.7
Yang Bin,Wang Haonan,Kong Jilie,Fang Xueen
Real-time and continuous monitoring of nucleic acid biomarkers with wearable devices holds potential for personal health management, especially in the context of pandemic surveillance or intensive care unit disease. However, achieving high sensitivity and long-term stability remains challenging. Here, we report a tetrahedral nanostructure-based Natronobacterium gregoryi Argonaute (NgAgo) for long-term stable monitoring of ultratrace unamplified nucleic acids (cell-free DNAs and RNAs) in vivo for sepsis on wearable device. This integrated wireless wearable consists of a flexible circuit board, a microneedle biosensor, and a stretchable epidermis patch with enrichment capability. We comprehensively investigate the recognition mechanism of nucleic acids by NgAgo/guide DNA and signal transformation within the Debye distance. In vivo experiments demonstrate the suitability for real-time monitoring of cell-free DNA and RNA with a sensitivity of 0.3 fM up to 14 days. These results provide a strategy for highly sensitive molecular recognition in vivo and for on-body detection of nucleic acid.
研究领域:
生物医学工程
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纳米技术
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分子生物学
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可穿戴设备
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健康监测
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
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IF 16.874
Ying Chen,Yonglin Wang,Xianfang Jiang,Jinhong Cai,Yuting Chen,Hanji Huang,Yuan Yang,Li Zheng,Jinmin Zhao,Ming Gao
Excessive cell-free DNA (cfDNA) released by damaged or apoptotic cells can cause inflammation, impacting the progression of rheumatoid arthritis (RA). cfDNA scavengers, such as cationic nanoparticles (NPs), have been demonstrated as an efficient strategy for treating RA. However, most scavengers are limited by unfavorable biocompatibility and poor scavenging efficacy. Herein, by exploiting the favorable biocompatibility, biodegradability and bioadhesion of polydopamine (P), we modified P with dimethylamino groups to form altered charged DPs to bind negatively charged cfDNA for RA therapy. Results showed that DPs endowed with superior binding affinity of cfDNA and little cytotoxicity, which effectively inhibited lipopolysaccharide (LPS) stimulated inflammation in vitro , resulting in the relief of joint swelling, synovial hyperplasia and cartilage destruction in RA rats. Significantly, DPs with higher DS of bis dimethylamino group exhibited higher positive charge density and stronger cfDNA binding affinity, leading to excellent RA therapeutic effect among all of the treated groups, which was even close to normal rats. These finding provides a novel strategy for the treatment of cfDNA-associated diseases.
研究领域:
纳米技术
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药学
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风湿病学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
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