Advanced Science
·
2023
·
IF 15.1
Hao Chen,Lina Guo,Jinsong Ding,Wenhu Zhou,Yan Qi
Gene therapy that employs therapeutic nucleic acids to modulate gene expression has shown great promise for diseases therapy, and its clinical application relies on the development of effective gene vector. Herein a novel gene delivery strategy by just using natural polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) as raw material is reported. EGCG first intercalates into nucleic acids to yield a complex, which then oxidizes and self-polymerizes to form tea polyphenols nanoparticles (TPNs) for effective nucleic acids encapsulation. This is a general method to load any types of nucleic acids with single or double strands and short or long sequences. Such TPNs-based vector achieves comparable gene loading capacity to commonly used cationic materials, but showing lower cytotoxicity. TPNs can effectively penetrate inside cells, escape from endo/lysosomes, and release nucleic acids in response to intracellular glutathione to exert biological functions. To demonstrate the in vivo application, an anti-caspase-3 small interfering ribonucleic acid is loaded into TPNs to treat concanavalin A-induced acute hepatitis, and excellent therapeutic efficacy is obtained in combination with the intrinsic activities of TPNs vector. This work provides a simple, versatile, and cost-effective gene delivery strategy. Given the biocompatibility and intrinsic biofunctions, this TPNs-based gene vector holds great potential to treat various diseases.
研究领域:
药学
·
纳米技术
·
分子生物学
·
基因治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Xiaotong Chen,Lianying Zhang,Haifeng Zeng,Wei Meng,Guijiang Liu,Wenhua Zhang,Pei Zhao,Qun Zhang,Ming Chen,Jinxiang Chen
Rheumatoid arthritis (RA) is a chronic autoimmune disease commonly associated with the accumulation of hyperactive immune cells (HICs), particularly macrophages of pro-inflammatory (M1) phenotype, accompanied by the elevated level of reactive oxygen species (ROS), decreased pH and O 2 content in joint synovium. In this work, an immunomodulatory nanosystem (IMN) is developed for RA therapy by modulating and restoring the function of HICs in inflamed tissues. Manganese tetraoxide nanoparticles (Mn 3 O 4 ) nanoparticles anchored on UiO-66-NH 2 are designed, and then the hybrid is coated with Mn-EGCG film, further wrapped with HA to obtain the final nanocomposite of UiO-66-NH 2 @Mn 3 O 4 /Mn-EGCG@HA (termed as UMnEH). When UMnEH diffuses to the inflammatory site of RA synovium, the stimulation of microwave (MW) irradiation and low pH trigger the slow dissociation of Mn-EGCG film. Then the endogenously overexpressed hydrogen peroxide (H 2 O 2 ) disintegrates the exposed Mn 3 O 4 NPs to promote ROS scavenging and O 2 generation. Assisted by MW irradiation, the elevated O 2 content in the RA microenvironment down-regulates the expression of hypoxia-inducible factor-1α (HIF-1α). Coupled with the clearance of ROS, it promotes the re-polarization of M1 phenotype macrophages into anti-inflammatory (M2) phenotype macrophages. Therefore, the multifunctional UMnEH nanoplatform, as the IMN, exhibits a promising potential to modulate and restore the function of HICs and has an exciting prospect in the treatment of RA.
研究领域:
纳米技术
·
免疫学
·
风湿病学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Wenhe Luo,Yanqiao Zeng,Qingle Song,Yu Wang,Feng Yuan,Qi Li,Yingnan Liu,Su Li,Nahar Jannatun,Guofang Zhang,Yang Li
Despite the success of immuno-oncology in clinical settings, the therapeutic efficacy is lower than the expectation due to the immunosuppressive inflammatory tumor microenvironment (TME) and the lack of functional lymphocytes caused by exhaustion. To enhance the efficacy of immuno-oncotherapy, a synergistic strategy should be used that can effectively improve the inflammatory TME and increase the tumor infiltration of cytotoxic T lymphocytes (CTLs). Herein, a TME hypoxia-responsive nanogel (NG) is developed to enhance the delivery and penetration of diacerein and (-)-epigallocatechin gallate (EGCG) in tumors. After systemic administration, diacerein effectively improves the tumor immunosuppressive condition through a reduction of MDSCs and Tregs in TME, and induces tumor cell apoptosis via the inhibition of IL-6/STAT3 signal pathway, realizing a strong antitumor effect. Additionally, EGCG can effectively inhibit the expression of PD-L1, restoring the tumor-killing function of CTLs. The infiltration of CTLs increases at the tumor site with activation of systemic immunity after the combination of TIM3 blockade therapy, ultimately resulting in a strong antitumor immune response. This study provides valuable insights for future research on eliciting effective antitumor immunity by suppressing adverse tumor inflammation. The feasible strategy proposed in this work may solve the urgent clinical concerns of the dissatisfactory checkpoint-based immuno-oncotherapy.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Fang Liu,Yaru Li,Yao Li,Zheng Wang,Xin Li,Yancheng Liu,Yanjun Zhao
The clinical translation of the anticancer drug β -lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe 3+ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways ( e.g ., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP’s therapeutic window via controlled cargo release and vehicle sensitization.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
·
细胞死亡机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Bo Zhang,Ruijuan Yao,Manfred F. Maitz,Genwen Mao,Zhe Hou,Hongchi Yu,Rifang Luo,Yunbing Wang
Controlled corrosion and proper biological response are key demands for biodegradable Mg-alloy based vascular stents. To achieve those properties, herein, a chemical conversion coating was fabricated through layer-by-layer (LBL) assembly via the sequential assembly of poly (dimethyl-diallyl ammonium chloride) (PDDA), epigallocatechin gallate (EGCG) and heparin (Hep). Each component in the coating played a unique role, in which EGCG chelates Mg ions and enhances the stability of the coating by introducing multiple intermolecular interactions, while PDDA effectively enhances the resistance against chloride corrosion, and Hep provides adequate hemocompatibility and promotes endothelialization. Electrochemical assay and immersion test demonstrated that the synergistic combination of PDDA and EGCG effectively suppressed the corrosion rate. A systematic in vitro and ex-vivo evaluation demonstrated an impressive antithrombotic performance, along with a selective promotion of endothelial cells (ECs) proliferation and inhibition of smooth muscle cells (SMCs) growth and macrophages (MAs) activation. More importantly, subcutaneous implantation and implantation in the abdominal aorta wall indicated that the PDDA/EGCG/Hep-modified implants displayed good corrosion resistance and mild tissue response, enhanced endothelialization and suppressed intima hyperplasia. These promising outcomes revealed the clinical potential of the PDDA/EGCG/Hep coating on AZ31 as biodegradable cardiovascular implants.
研究领域:
材料科学
·
生物医学工程
·
腐蚀科学
·
组织工程
·
心血管植入物
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Hui Shi,Ru Wang,Hu-Chen Cao,Hai-Yan Guo,Pei Pan,Cheng-Feng Xiong,Lin-Jun Zhang,Qiang Yang,Shuang Wei,Tao Liu
To overcome the limitations of doxorubicin (DOX) chemotherapy, nanomedicines that integrate additional photothermal therapy (PTT) and chemodynamic therapy (CDT) strategies are highlighted as promising alternatives for the treatment of malignant tumors. However, time-consuming preparation processes, biosafety concerns, and the bottlenecks of individual therapeutic modalities often limit the practical applications of this strategy. To address these issues, this work designs an oxygen economizer that additionally serves as a Fenton reaction amplifier through the simple assembly of epigallocatechin gallate (EGCG), pluronic F-127 (PF127), iron (III) ions, and doxorubicin (DOX) for the enhancement of synergistic PTT/CDT/chemotherapy. The resulting nanoformulation, EFPD, can target mitochondria and inhibit cell respiration to reduce O 2 consumption, thus boosting DOX-mediated H 2 O 2 generation for enhanced CDT and simultaneously improving hypoxia-limited DOX chemotherapy efficacy. Moreover, the coordination between EGCG and Fe 3+ provides EFPD with excellent photothermal conversion efficiencies ( η = 34.7%) for PTT and photothermal-accelerated drug release. Experimental results indicate that EFPD-mediated synergistic enhancement of PTT/CDT/chemotherapy can achieve excellent therapeutic outcomes, including enhanced ablation of solid tumors, reduced metastasis and cardiotoxicity, and extended life spans.
研究领域:
纳米医学
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Yao Li,Mengying Liu,Yan Zheng,Zheng Wang,Yanjun Zhao
Cancer cells show unique redox homeostasis . Glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play essential roles as coenzymes of multiple key antioxidant enzymes. Coenzyme depletion offers a unique opportunity for cancer treatment by inducing oxidative stress . Here, we report an innovative hybrid nanocarrier for cancer redox therapy via selective depletion of GSH and NADPH. The nanocarrier core is a sorafenib-loaded porous zeolitic imidazole framework (ZIF-65), and the shell is epigallocatechin gallate (EGCG)-Fe 3+ complex (EF). The nitroimidazole ligand in ZIF-65 could selectively deplete NADPH under hypoxia . Sorafenib diminished GSH by inhibiting cystine import and GSH biosynthesis. EGCG can reduce Fe 3+ to Fe 2+ , which aids the generation of hydroxyl radicals via the Fenton reaction . The reversible coordination between nitroimidazole and Zn 2+ , EGCG, and Fe 3+ enables triggered cargo release in acidic lysosomes . Tailored nanocarriers induced the depletion of both coenzymes (GSH and NADPH) and boosted reactive oxygen species in a 4T1 murine cancer cell line. The altered redox balance eventually resulted in efficient apoptotic cell death. The current work offers a novel means of redox cancer therapy via the selective depletion of key antioxidant enzymes in hypoxic cells.
研究领域:
癌症治疗
·
纳米技术
·
氧化还原生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Qingyu Yu,Hong Sun,Linhua Zhang,Lijie Jiang,Lei Liang,Chaojie Yu,Xiaoru Dong,Bingyan Guo,Yuwei Qiu,Jingwu Li,Hong Zhang,Fanglian Yao,Dunwan Zhu,Junjie Li
Postoperative peritoneal adhesion is a serious clinical complication. Various hydrogel barriers have been developed to prevent peritoneal adhesion. However, it remains a challenge to design a hydrogel with desirable physicochemical properties and bioactivities. In this study, a zwitterionic polysaccharide-based multifunctional hydrogel is developed using epigallocatechin-3-gallate (EGCG) to prevent postoperative abdominal adhesion. This hydrogel is simple to use and has desirable properties, such as excellent injectability, self-healing, and non-swelling properties. The hydrogel also has ultralow fouling capabilities, such as superior bactericidal performance, cell and protein adhesion, and low immunogenicity resistance. Moreover, the hydrogel exhibits good antioxidant activity, which is attributed to the integration of EGCG. Furthermore, the detailed mechanism from in vivo and in vitro experimental studies illustrates that hydrogel compositions can synergistically prevent adhesion formation through multiple pathways, including anti-inflammatory and antioxidant capabilities and inhibition effects on the mesothelial-mesenchymal transition (MMT) process induced by transforming growth factor (TGF-β). In summary, this zwitterionic multifunctional hydrogel has great potential to prevent postoperative adhesion formation in the clinical setting.
研究领域:
生物医学工程
·
材料科学
·
药剂学
·
外科手术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2016
·
IF 3.973
Yu Zhang,Shiguo Chen,Chaoyang Wei,Jianchu Chen,Xingqian Ye
The increasing rate of hyperlipidemia has drawn great attention and natural products may play a potential role in prevention of these disorders. Chinese bayberry leaves proanthocyanidin (BLPs) with epigallocatechin-3- O -gallate (EGCG) as its terminal and major extension units is unusual in the plant kingdom. Crude, purified and ultrasound depolymerized BLPs (CBLPs, SPBLPs and UDBLPs) were prepared with the aim to investigate their hypolipidemic mechanisms. BLPs inhibited the lipase activity in vitro and reduced the accumulation of total triacylglycerols (TAG) and cholesterol induced by oleic acid in HepG2 cells. SPBLPs and UDBLPS significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and thus reduced TAG and sterols biosynthesis by inhibiting its downstream proteins, such as acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element-binding protein. BLPs also promoted glucose consumption in oleic acid induced HepG2 cells. Overall, this study suggests the hypolipidemic property and promotion of glucose consumption of BLPs via AMPK pathway.
研究领域:
药理学
·
营养学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Zhiqing Liu,Tianlong Wang,Lei Zhang,Yiping Luo,Jinhui Zhao,Yixing Chen,Yao Wang,Wentao Cao,Xinyu Zhao,Bingqiang Lu,Feng Chen,Zifei Zhou,Longpo Zheng
The limited regulation strategies of the regeneration microenvironment significantly hinder bone defect repair effectiveness. One potential solution is using biomaterials capable of releasing bioactive ions and biomolecules. However, most existing biomaterials lack real-time control features, failing to meet high regulation requirements. Herein, a new Strontium (Sr) and epigallocatechin-3-gallate (EGCG) based metal–phenolic network with polydopamine (PMPNs) modification is prepared. This material reinforces a biomimetic scaffold made of extracellular matrix (ECM) and hydroxyapatite nanowires (nHAW). The PMPNs@ECM/nHAW scaffold demonstrates exceptional scavenging of free radicals and reactive oxygen species (ROS), promoting HUVECs cell migration and angiogenesis, inducing stem cell osteogenic differentiation, and displaying high biocompatibility. Additionally, the PMPNs exhibit excellent photothermal properties, further enhancing the scaffold's bioactivities. In vivo studies confirm that PMPNs@ECM/nHAW with near-infrared (NIR) stimulation significantly promotes angiogenesis and osteogenesis, effectively regulating the microenvironment and facilitating bone tissue repair. This research not only provides a biomimetic scaffold for bone regeneration but also introduces a novel strategy for designing advanced biomaterials. The combination of real-time photothermal intervention and long-term chemical intervention, achieved through the release of bioactive molecules/ions, represents a promising direction for future biomaterial development.
研究领域:
生物材料
·
组织工程
·
骨再生
·
光热疗法
·
血管生成
·
成骨
·
生物相容性
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Huining Wan,Xiaohui Yang,Yutong Zhang,Xiyu Liu,Yanyan Li,Yumei Qin,Hui Yan,Lan Gui,Ke Li,Longjian Zhang,Li Yang,Bo Zhang,Yunbing Wang
Although minimally invasive interventional occluders can effectively seal heart defect tissue, they still have some limitations, including poor endothelial healing, intense inflammatory response, and thrombosis formation. Herein, a polyphenol-reinforced medicine/peptide glycocalyx-like coating was prepared on cardiac occluders. A coating consisting of carboxylated chitosan, epigallocatechin-3-gallate (EGCG), tanshinone IIA sulfonic sodium (TSS), and hyaluronic acid grafted with 3-aminophenylboronic acid was prepared. Subsequently, the mercaptopropionic acid-GGGGG-Arg-Glu-Asp-Val peptide was grafted by the thiol–ene “click” reaction. The coating showed good hydrophilicity and free radical-scavenging ability and could release EGCG–TSS. The results of biological experiments suggested that the coating could reduce thrombosis by promoting endothelialization, and promote myocardial repair by regulating the inflammatory response. The functions of regulating cardiomyocyte apoptosis and metabolism were confirmed, and the inflammatory regulatory functions of the coating were mainly dependent on the NF-kappa B and TNF signaling pathway.
研究领域:
心脏病学
·
生物医学工程
·
材料科学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
·
2022
·
IF 6.443
Xin Luo,Jiankang Lu,Yongyan Wu,Wenshan Duan,Fengping An,Qun Huang,Lei Chen,Shaofeng Wei
Potential allergenicity of amandin was reduced by binding amandin with (−)-epigallocatechin gallate (EGCG) via alkaline, free radical, ultrasound-assisted alkaline, and ultrasound-assisted free radical methods. These results of total phenol content, free sulfhydryl group, free amino group, surface hydrophobicity, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) indicated that amandin might be covalently bound to EGCG through reactive groups such as sulfhydryl and amino groups, or non-covalently through hydrophobic interactions. Fourier transformed infrared (FT-IR) spectroscopy and fluorescence spectroscopy revealed structural changes of amandin-EGCG conjugate, which also caused significant reduction in potential allergenicity of amandin. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) found that amandin bound to EGCG mainly through cysteine and glutamate residues, and linear epitope for amandin was reduced. This provided a new method and theoretical basis of hypoallergenic almond food.
研究领域:
食品科学
·
过敏学
·
化学
·
生物化学
✓ 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）