JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Ying Zhang,Shiqi Lin,Xiao Xu,Yufan Yao,Shufan Feng,Sida Jiang,Yuqian Wang,Wei He,Ran Mo
Dysregulation of growth factor expression causes impaired healing of diabetic foot ulcer (DFU). Platelet-derived growth factor (PDGF)-containing gel has been clinically applied for topical treatment of DFU. Recruitment of neutrophils stimulated by PDGF favors the wound healing of DFU. However, overactivation of neutrophils induced by hyperglycemia causes massive generation and long-term persistence of neutrophil extracellular traps (NETs), ultimately leading to unexpected skin damage and delayed wound repair. Here, we engineer a hierarchically-assembled hydrogel to achieve local release of the growth factor, PDGF-BB and the NET scavenger, deoxyribonuclease (DNase) I with distinct kinetics for enhanced healing of DFU. The hydrogel is constructed by crosslinking of anti-bacterial quaternized chitosan and hypochlorite-degradable nanogel via a copper-free click reaction, in which PDGF-BB is loaded in the hydrogel matrix while DNase I is encapsulated in the inner nanogel. Programmable release of combinatorial therapeutics is implemented by the hydrogel in response to the wound microenvironment. We show that the hierarchical hydrogel co-loaded with PDGF-BB and DNase I promotes neutrophil recruitment, increases endothelial cell migration, degrades excess NETs, and prevents wound infection for accelerating the wound closure in the diabetic mouse wound models.
研究领域:
生物材料学
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医学工程
·
再生医学
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DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-13
·
IF 3.9
Xia Meng,Cao Shisheng,Liu Zeqi,Zhao Jiakang,Yuan Yibo,Ni Jianhui,Guo Zhengjian,Wang Weihan,Yin Huijuan,Zou Zhaohui
Persistent or refractory apical periodontitis is primarily caused by microbial retention, as conventional root canal treatment often fails to eliminate infections completely, and systemic antibiotic therapy is insufficient to achieve effective concentrations for eradicating bacterial biofilms within root canals. This highlights the urgent need for novel therapeutics offering safe and effective antimicrobial strategies. Antimicrobial photodynamic therapy (aPDT) is a promising approach for root canal disinfection. However, commonly used photosensitizers such as Ce6 suffer from poor water solubility and strong aggregation tendencies, resulting in limited penetration into infected sites. In this study, we developed a DNase I-Lip@Ce6 nanodelivery system by combining deoxyribonuclease I (DNase I) with liposome-encapsulated Ce6. The liposomal carrier facilitated efficient delivery of Ce6 into target bacterial cells, while DNase I degraded extracellular DNA in the biofilm matrix, weakening its protective barrier. This synergistically enhanced Ce6 penetration and therapeutic efficacy, leading to the successful eradication of planktonic Enterococcus faecalis and in vitro biofilms. This strategy offers a novel approach for the precision treatment of persistent oral infections and holds strong potential for clinical translation.
研究领域:
口腔医学
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微生物学
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药剂学
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生物材料
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2017
·
IF 5.401
Bi-Yun Fang,Chun-Yuan Wang,Cheng Li,Hai-Bo Wang,Yuan-Di Zhao
In this paper, we proposed an amplified assay using DNase I for sensitively sensing prostate specific antigen (PSA) based on CdSe/ZnS quantum dot labelled PSA aptamer/graphene oxide (QD-aptamer/GO). In this sensing system, GO could strongly bind QD conjugated aptamer and quench the fluorescence of QD, furthermore, GO could protect DNA from nuclease cleavage. When binding target PSA, aptamer probe released from the surface of GO nanosheet, then the free aptamer could be cleaved by nuclease, thus the QD and PSA were liberated, after that, the released PSA would bind another aptamer on GO nanosheet and start a new cycle, which resulted in amplification of restoring signal. The probe possessed steady fluorescence signal and high specificity due to the anti photobleaching of QD and the high affinity of aptamer to PSA. Under the optimum experimental conditions, fluorescence intensity increased linearly with the PSA concentration between 0.1 fg mL −1 and 3 fg mL −1 with the limit of quantification of 0.05 fg mL −1 , which was three orders of magnitude lower than that without DNase I. Finally, the method was applied to quantification of PSA in human serum samples.
研究领域:
生物传感器
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分析化学
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纳米技术
·
癌症诊断
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Shuang Tian,Linzhu Su,Yingli An,Henny C. van der Mei,Yijin Ren,Henk J. Busscher,Linqi Shi
DNase can break down the extracellular matrix that keeps infectious bacterial biofilm together through cleavage of eDNA. Herewith, biofilm bacteria can become dispersed to assist antibiotic eradication but this has hitherto remained an in vitro possibility. In vivo DNase is rapidly broken down in blood, impeding blood-injection of DNase combined with antibiotics to cure bacterial infections. Herein, we report the synthesis of pH-responsive, self-targeting micelles self-assembled from a solution of poly(ethylene glycol)- block -poly(ε-caprolactone) (PEG- b -PCL) and poly(ε-caprolactone)- block -poly(amino ester) (PCL- b -PAE) with DNase conjugated to PAE-blocks. At physiological pH, this conjugation protected DNase inside the micellar shell, while PEG prevented adsorption of blood-borne proteins to the micelles. PAE became positively-charged below pH 6.4 facilitating self-targeting to an infectious biofilm. Simultaneously, PAE became hydrophilic and stretched to expose DNase upon accumulation in an infectious S. aureus biofilm where it degraded the biofilm matrix. PEG/PAE-DNase micelles internally core-loaded with ciprofloxacin significantly better eradicated murine pneumonia after blood-injection than ciprofloxacin-loaded PEG/PAE micelles without conjugated DNase or ciprofloxacin free in solution. Considering that DNase is clinically approved for use in cystic fibrosis patients, this paves the way for clinical translation of ciprofloxacin-loaded, PEG/PAE-DNase micelles for the treatment of pneumonia and other infections that can be reached through self-targeting after blood-injection.
研究领域:
药学
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生物医学工程
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微生物学
·
药物递送系统
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DOI
高影响因子
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
·
2022
·
IF 4.175
Qing Liu,Xin Fang,Zeng-Ping Chen,Cai-Xia Shi,Ru-Qin Yu
Herein, the hydrolysis patterns of DNase I against a DNA probe in both single-strand form and DNA/miRNA heteroduplex were experimentally investigated in detail by mass spectrometric technique. Based on the knowledge obtained in the experiments, DNase I-assisted signal amplification strategy was proposed and used to design a mass spectrometric platform for miRNA detection. As a proof of concept, the performance of the proposed platform was evaluated for the detection of miRNA-122 in cell lysate samples. An advanced calibration model was explicitly derived to model the relationships between the concentration of miRNA-122 and the mass spectral signals of mass spectrometrically detected fragments of the DNA probe produced in the DNase I-assisted signal amplification process. With the aid of the advanced calibration model, the proposed mass spectrometric platform achieved quite accurate quantification results for miRNA-122 in cell lysate samples of Huh-7 and HepG-2 cell lines with recovery rates ranging from 98% to 104%. It is noteworthy that the proposed mass spectrometric platform can differentiate the target miRNA from other non-target ones based on their mass spectral response patterns instead of mass spectral intensities, and hence possesses high specificity for the target miRNA. It is reasonable to expect that the combination of mass spectrometry based on DNase I-assisted signal amplification with the advanced chemometric model provides a competitive alternative for designing cost-effective and label-free miRNA detection methods.
研究领域:
生物化学
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分子生物学
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分析化学
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DOI
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Yuchao Sun,Jian He,Weiyu Chen,Yongfang Wang,Kai Wang,Min Zhou,Yichun Zheng
High-dose radiation therapy is a widely used clinical strategy to inhibit tumor growth. However, the rapid generation of excessive reactive oxygen species (ROS) triggers the formation of neutrophil extracellular traps (NETs), which capture free tumor cells in the bloodstream, promoting metastasis. In this study, we developed a hybrid nanoparticle composed of DNase I and gold (DNase I@Au) to enhance radiotherapy efficacy while mitigating metastasis by precisely eliminating NETs. The DNase I@Au nanoparticles, administered via aerosol inhalation, are efficiently delivered to lung tumor tissue, improving radiosensitization and reducing tumor size. Crucially, the nanoparticles could gradually release DNase I, effectively degrading ROS-induced NETs and preventing the interaction of free malignant cells with tumor sites or vasculature, thereby inhibiting metastasis. Therefore, we provide an enzyme and sensitizer co-loaded strategy that offers a promising approach to improve the therapeutic outcome of radiotherapy and reduce the risk of lung cancer metastasis under ROS stimulation.
研究领域:
肿瘤学
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纳米技术
·
放射生物学
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药学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Yuxue Pan,Mengyuan Wang,Peng Wang,Hongliang Wei,Xiangjuan Wei,Dongmei Wang,Yongwei Hao,Yongxue Wang,Hongli Chen
Oral mucositis (OM) is a common side effect experienced by cancer patients undergoing chemotherapy and/or radiotherapy. In this study, we developed a semi-interpenetrating network hydrogel (IPN) that is suitable for adhesion to oral mucous membranes and gradual degradation in the oral environment. This IPN was based on the combination of ε-polylysine (PLL) and Hetastarch (HES), loaded with DNase-I and Oridonin (ORI) (ORI/DNase-I/IPN) for the treatment of OM. In vitro studies were conducted to evaluate degradation, adhesion, release analysis, as well as bioactivity including cell proliferation and wound healing assays using epidermal keratinocyte and fibroblast cell lines. Furthermore, the therapeutic effects of ORI/DNase-I/IPN were investigated in vivo using Sprague-Dawley (SD) rats with chemoradiotherapy-induced OM. The results demonstrated that the IPN exhibited excellent adhesion to wet mucous membranes, and the two drugs co-encapsulated in the hydrogel were released in a controlled manner. The in vivo wound repair effect, microbiological assays, H&E and Masson staining supported the non-toxicity of ORI/DNase-I/IPN, as well as its ability to accelerate the healing of oral ulcers and reduce inflammation. Overall, ORI/DNase-I/IPN demonstrated a therapeutic effect on oral ulcers in rats by significantly accelerating the healing process and reducing inflammation. These findings provide new insights into possible therapies for OM.
研究领域:
药学
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生物医学工程
·
癌症研究
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药物递送系统
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组织工程
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·Vol. 33
·期 19
·2213465
·
IF 19
Huiyi Liang,Yibo Du,Lixin Liu,Junqiu Liu,Yongming Chen
Excessive self-DNAs recognized by intracellular DNA sensors can initiate innate immunity to express disordered TNF-α or type I IFN resulting in several autoimmune diseases. Cationic polymers have been profoundly proved to alleviate the inflammatory symptoms by removing the debris of cell-free DNA (cfDNA). However, clinical applications of cationic materials have been impeded by concerns of their toxicity and the fate of cfDNA in polymer-cfDNA complex. Herein, it is showed that PEGylated polyimidazoles as a biomimetic DNase potently alleviate pathologic symptoms of self-DNA-associated rheumatoid arthritis (RA) rats and Trex1 (DNase III) deficient Aicardi-Goutiéres syndrome (AGS) mice. The mechanism studies demonstrate that the polyimidazole efficiently attacks the phosphodiester linkages of NAs and cleavages them into small pieces. As imidazole unit is a much weaker organic base that occurs in natural proteins, the polyimidazoles are less toxic to cells and tissues, as manifested by the IC50 values larger than 1000 µg mL −1 . This work suggests that synthetic tailored DNase can be a new and safe therapeutic agent to treat chronic autoimmune and refractory inflammatory diseases by degradation of excessive nucleic acids.
研究领域:
免疫学
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生物医学工程
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分子生物学
·
药理学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xuan He,Dan Liang,Jun Zhou,Kangjing Li,Beibei Xie,Chunyun Liang,Cong Liu,Zhiyong Chen,Xinxin Chen,Ao Long,Shufang Zhuo,Xiaoping Su,Ying Luo,Wenxia Chen,Fengfeng Zhao,Xinglu Jiang
The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy.
研究领域:
癌症研究
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药物递送系统
·
纳米技术
·
生物医学工程
·
药学
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产品关联
DOI
PubMed
高影响因子
FOOD CONTROL
·
2023
·
IF 6
Chenfei Han,Yu Xiao,Zhenjiang Liu,Daolin Du,Ming Li
To improve the performance of aptasensor, the coupling of novel material and strategy had been the hottest research with the promising prospects. In this study, a cascade amplifying aptasensor (CA-aptasensor), which had coupled the DNase I-assisted cyclic enzyme digestion and AgNPs@gel-enhanced fluorescence, had reflected the desired performance for positively correlated detecting OTA . For this purpose, the GO@PVP was used to adsorb and quench the free FAM-Apt, while the complex of OTA and FAM-Apt was digested by the DNase I. The released OTA allowed the free FAM-Apt to separate from the GO@PVP cyclically, thus the OTA level was amplified preliminarily. The AgNPs@gel could combine with the released FAM to form the metal enhanced fluorescence (MEF) effect, resulting in the cascade signal amplification. The OTA was detected at pg mL −1 level with an ultrasensitive LOD of 3.33 pg mL −1 and IC 50 of 13.6 pg mL −1 , which improved 90-fold and 728-fold than that of ELASA for same aptamer. The CA-aptasensor indicated high specificity, reliability and practicability. Meanwhile, the CA-aptasensor exhibited more highlights, including the efficient homogeneous system, low background signal and standardized aptamer recognizer. This study might provide a new approach for improving the performance of aptasensor, which could also guide the signaling cascade and positively correlated detection for other risk factors.
研究领域:
分析化学
·
生物传感器
·
纳米技术
·
食品安全
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产品关联
DOI
高影响因子
TALANTA
·
2025
·
IF 6.1
Yafang Shen,Xingyue Tang,Jiangqi Wang,Huang Dai,Yanna Cui,Qiuyue Hu,Yuxin Wu,Fei Jia,Guijie Hao
Recent years have witnessed the flourishing of CRISPR/Cas-based biosensors in various fields. However, most of them were developed for nucleic acid detection because non-nucleic acid targets are unable to unleash the cleavage activity of the CRISPR/Cas system directly. To circumvent this problem, activator DNA and deoxyribonuclease I (DNase I) were introduced in this research to render the CRISPR/Cas12a system as a new powerful tool for the detection of enrofloxacin (ENR), a common veterinary drug. In this biosensor, target ENR competed with DNase I- and bovine serum albumin-ENR composite-modified gold nanoparticles (DNase I-AuNPs-BSA-ENR) for the binding sites on the surface of antibody-modified magnetic nanoparticles (immuno-MNPs). Then, the captured DNase I-AuNPs-BSA-ENR degraded the activator DNA in the solution, which inhibited the activation of the CRISPR/Cas12a system. Finally, the fluorescence released by the activated CRISPR/Cas12a system was measured for the quantitative detection of ENR. The ingenious use of activator DNA and DNase I helped transduce the target recognition event into the cleavage activity of the CRISPR/Cas12a system. Moreover, the dual enzymatic amplification from DNase I and the CRISPR/Cas12a system guaranteed the sensitivity of this method with a low detection limit of 0.04 ng/mL. The developed biosensor extended the application of the CRISPR/Cas12a system for the sensitive detection of non-nucleic acid targets, providing a powerful tool in various fields such as environmental monitoring, food safety and clinical diagnosis.
研究领域:
生物技术
·
食品安全
·
环境监测
·
临床诊断
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 11.5
Ping Li,Qianying Li,Lu Ding,Wan Zhang,Shiyu Peng,Hui Wei,Xuanqi Zhao,Tingtao Chen,Yonghua Xiong,Benzhong Tang,Xiaolin Huang
Bacteria are emerging as a promising tool for targeted cancer therapy due to their innate tumor-homing ability, high mobility, and capacity to rapidly colonize in the tumor microenvironment (TME). However, bacterial cancer therapy (BCT) alone has not proven fully effective. Herein, we present an innovative bio-therapeutic system, TEPy@VNP-D, which integrates genetically engineered Salmonella typhimurium VNP20009 carrying humanized DNase I toxin plasmids (VNP-D) with an aggregation-induced emission photosensitizer (TEPy), enabling photoimmunotherapy for melanoma. Leveraging the tumor-targeting properties of VNP20009, TEPy@VNP-D ensures effective delivery of both TEPy and DNase I to tumor sites, promoting the intratumoral accumulation of cytotoxic agents. Upon light activation, TEPy@VNP-D not only disrupts bacterial structures, facilitating plasmid release but also directly kills cancer cells through the generation of cytotoxic reactive oxygen species. Accordingly, the synergistic effects of photodynamic therapy (PDT) from TEPy and tumor lysis by VNP-D result in significant tumor suppression. Furthermore, TEPy@VNP-D enhances both innate and adaptive immune responses by triggering immunogenic cell death and remodeling the immunosuppressive TME. When combined with anti-PD-L1 antibody, TEPy@VNP-D elicits remarkable synergistic effects under light irradiation, effectively eliminating distant abscopal tumors and establishing robust immune memory to prevent recurrence and rechallenge. Together, the TEPy@VNP-D-mediated BCT synergized photoimmunotherapy strategy offers a powerful, tailored approach to cancer treatment, achieving cooperative antitumor activity with reduced toxicity. This promising approach holds great potential for advancing combination cancer therapies.
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PubMed
高影响因子
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