Advanced Science
·
2020
·Vol. 7
·期 12
·1902933
·
IF 15.84
Jiaojiao Wu,Peng Ning,Rui Gao,Qishuai Feng,Yajing Shen,Yifan Zhang,Yingze Li,Chang Xu,Yao Qin,Gustavo R. Plaza,Qianwen Bai,Xing Fan,Zhenguang Li,Yu Han,Maciej S. Lesniak,Haiming Fan,Yu Cheng
Reactive oxygen species (ROS), a group of oxygen derived radicals and derivatives, can induce cancer cell death via elevated oxidative stress. A spatiotemporal approach with safe and deep-tissue penetration capabilities to elevate the intracellular ROS level is highly desirable for precise cancer treatment. Here, a mechanical-thermal induction therapy (MTIT) strategy is developed for a programmable increase of ROS levels in cancer cells via assembly of magnetic nanocubes integrated with alternating magnetic fields. The magneto-based mechanical and thermal stimuli can disrupt the lysosomes, which sequentially induce the dysfunction of mitochondria. Importantly, intracellular ROS concentrations are responsive to the magneto-triggers and play a key role for synergistic cancer treatment. In vivo experiments reveal the effectiveness of MTIT for efficient eradication of glioma and breast cancer. By remote control of the force and heat using magnetic nanocubes, MTIT is a promising physical approach to trigger the biochemical responses for precise cancer treatment.
研究领域:
生物医学工程
·
癌症研究
·
纳米技术
·
诊疗学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 45
·7141-7151
·
IF 5.047
Jun Zhang,Tiantian Zuo,Xiao Liang,Yingxin Xu,Yifan Yang,Tianxu Fang,Jing Li,Daijie Chen,Qi Shen
Triple-negative breast cancer (TNBC) is characterized by a high metastatic rate, which can seriously threaten women's health. ROS play an important role in tumor development and metastasis. Excessive ROS can induce tumor cell apoptosis and inhibit tumor cell metastasis. This study investigated Fenton-reaction-stimulative nanoparticles (P@P/H NPs) containing ROS-responsive molecular switches for antitumor metastasis by amplifying the ROS and activating the cascade biological reaction of ROS in tumor cells. Spheroidal P@P/H NPs exhibited a uniform size of 68.18 ± 0.29 nm, high drug cumulative release of 97.59% in response to H2O2 at 24 h, and satisfactory cytotoxicity with the IC50 value of 0.50 ± 0.02 μg mL−1. The markedly elevated ROS level caused by P@P/H NPs generated an evident antitumor metastasis effect in vitro by facilitating the expressions of cytochrome c, caspase-9, and caspase-3 and blocking that of matrix metalloprotein 9 (MMP-9). Moreover, P@P/H NPs engendered an excellent tumor inhibition rate of 56.37% and antitumor metastasis effect in vivo. Therefore, P@P/H NPs could respond to H2O2 in tumor cells to rapidly disassemble and further increase the ROS to induce antitumor metastasis via the Fenton reaction.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Yinuo Tu,Yuping Zhou,Di Zhang,Jinghong Yang,Xiang Li,Kaiyuan Ji,Xu Wu,Ruiyuan Liu,Qianbing Zhang
Mitochondria are identified as a valuable target for cancer therapy owing to their primary function in energy supply and cellular signal regulation. Mitochondria in tumor cells are depicted by excess reactive oxygen species (ROS), which lead to numerous detrimental results. Hence, mitochondria-targeting ROS-associated therapy is an optional therapeutic strategy for cancer. In this contribution, a light-induced ROS generator (TBTP) is developed for evaluation of the efficacy of mitochondria-targeting ROS-associated therapy and investigation of the mechanism underlying mitochondrial-injure-mediated therapy of tumors. TBTP serves as an efficient ROS generator with low cytotoxicity, favorable biocompatibility, excellent photostability, mitochondria-targeted properties, and NIR emission. In vivo and in vitro experiments reveal that TBTP exhibits effective anticancer potential. ROS generated from TBTP could destroy the integrity of mitochondria, downregulate ATP, decrease the mitochondrial membrane potential, secrete Cyt-c into cytoplasm, activate Caspase-3/9, and induce cell apoptosis. Moreover, RNA-seq analysis highlights that an ROS burst in mitochondria can kill tumor cells via inhibition of the AKT pathway. All these results prove that mitochondrial-targeted ROS-associated therapy hold great potential in cancer therapy.
研究领域:
肿瘤学
·
分子生物学
·
治疗科学
✓ 已验证
产品关联
DOI
PubMed
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Chen Junyi,Wang Huan,Wang Jinlin,Zheng Xixi,Qu Wantong,Fang Huijian,Wang Shuang,He Le,Hao Shuang,Dresselhaus Thomas
Fertilization-dependent elimination of the persistent synergid cell is essential to block supernumerary pollen tubes and thus to avoid polyspermy in flowering plants. Little is known about the molecular mechanisms ensuring timely induction and execution of synergid cell death. We analyzed manually isolated maize synergid cells along their degeneration and show that they are gland cells expressing batteries of genes encoding small secreted proteins under control of the MYB98 transcription factor. This network is down-regulated after fertilization, while genes involved in reactive oxygen species (ROS) production, ethylene biosynthesis and response, senescence, and oxidative stress regulation are induced before synergid elimination and its ultimate fusion with the endosperm. We further show that the fertilization-induced RALF12 peptide specifically triggers mitochondrial ROS and apoptosis, while ethylene promotes synergid degeneration. In conclusion, this study sheds light on developmental programmed cell death (dPCD) in plants and provides a unique resource to discover unknown PCD regulators.
研究领域:
植物学
·
分子生物学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2025
·
IF 4.2
Guoqiang Fan,Yaxin Liu,Limei Tao,Danping Wang,Yizhu Huang,Xiaojing Yang
Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with unclear causes and limited treatment options. Sodium butyrate (NaB), a byproduct of dietary fiber in the intestine, has demonstrated efficacy in treating inflammation. However, the precise anti-inflammatory mechanisms of NaB in colon inflammation remain largely unexplored. This study aims to investigate the effects of NaB on dextran sulfate sodium (DSS)-induced colitis in rats. The findings indicate that oral administration of NaB effectively prevent colitis and reduce levels of serum or colon inflammatory factors. Additionally, NaB demonstrated in vitro inhibition of RAW264.7 inflammation cytokines induced by LPS, along with suppression of the ERK and NF-κB signaling pathway activation. Moreover, NaB mitigated LPS and Nigericin-induced RAW264.7 pyroptosis by reducing indicators of mitochondrial damage, including increased mitochondrial membrane potential (JC-1) levels and decreased Mito-ROS production. NaB increases ZO-1 and Occludin expression in CaCo2 cells by inhibiting RAW264.7 pyroptosis. These results suggest that NaB could be utilized as a therapeutic agent or dietary supplement to alleviate colitis.
研究领域:
免疫学
·
消化病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomaterials
·
2024
·Vol. 14
·期 5
·389
·
IF 4.4
Feng Gao,Wenyu Liang,Qixin Chen,Bairu Chen,Yuchen Liu,Zhibo Liu,Xu Xu,Rongrong Zhu,Liming Cheng
Disordered reactive oxygen/nitrogen species are a common occurrence in various diseases, which usually cause cellular oxidative damage and inflammation. Despite the wide range of applications for biomimetic nanoparticles with antioxidant or anti-inflammatory properties, designs that seamlessly integrate these two abilities with a synergistic effect in a simple manner are seldom reported. In this study, we developed a novel PEI-Mn composite nanoparticle (PM NP) using a chelation method, and the curcumin was loaded onto PM NPs via metal–phenol coordination to form PEI-Mn@curcumin nanoparticles (PMC NPs). PMC NPs possessed excellent dispersibility and cytocompatibility, was engineered to serve as an effective nanozyme, and exhibited specific SOD-like and CAT-like activities. In addition, the incorporation of curcumin granted PMC NPs the ability to effectively suppress the expression of inflammatory cytokines in microglia induced by LPS. As curcumin also has antioxidant properties, it further amplified the synergistic efficiency of ROS scavenging. Significantly, PMC NPs effectively scavenged ROS triggered by H2O2in SIM-A9 microglia cells and Neuro-2a cells. PMC NPs also considerably mitigated DNA and lipid oxidation in Neuro-2a cells and demonstrated an increase in cell viability under various H2O2concentrations. These properties suggest that PMC NPs have significant potential in addressing excessive ROS and inflammation related to neural diseases.Keywords:nanozyme;ROS scavenging;anti-inflammatory;neuroprotective
研究领域:
纳米技术
·
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Qigu Yao,Beiduo Wang,Jiong Yu,Qiaoling Pan,Yingduo Yu,Xudong Feng,Wenyi Chen,Jinfeng Yang,Changyou Gao,Hongcui Cao
Primary sclerosing cholangitis (PSC) is a challenging cholestatic liver disease marked by progressive bile duct inflammation and fibrosis that has no FDA-approved therapy. Although obeticholic acid (OCA) has been sanctioned for PSC, its clinical utility in PSC is constrained by its potential hepatotoxicity. Here, we introduce a novel therapeutic construct consisting of OCA encapsulated within a reactive oxygen species (ROS)-responsive, biodegradable polymer, further cloaked with human placenta-derived mesenchymal stem cell (hP-MSC) membrane (MPPFTU@OCA). Using PSC patient-derived organoid models, we assessed its cellular uptake and cytotoxicity. Moreover, using a PSC mouse model induced by 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC), we demonstrated that intravenous administration of MPPFTU@OCA not only improved cholestasis via the FXR-SHP pathway but also reduced macrophage infiltration and the accumulation of intracellular ROS, and alleviated mitochondria-induced apoptosis. Finally, we verified the ability of MPPFTU@OCA to inhibit mitochondrial ROS thereby alleviating apoptosis by measuring the mitochondrial adenosine triphosphate (ATP) concentration, ROS levels, and membrane potential (ΔΨm) using H 2 O 2 -stimulated PSC-derived organoids. These results illuminate the synergistic benefits of integrating an ROS-responsive biomimetic platform with OCA, offering a promising therapeutic avenue for PSC.
研究领域:
药理学
·
肝病学
·
纳米技术
·
干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2023
·
IF 6.7
Yu Ran,Shanmei Yin,Pei Xie,Yaxue Liu,ying wang,Zongning Yin
Acute Lung Injury (ALI) is an inflammatory disease caused by multiple factors such as infection, trauma, and chemicals. Without effective intervention during the early stages, it usually quickly progresses to acute respiratory distress syndrome (ARDS). Since ordinary pharmaceutical preparations cannot precisely target to the lungs, their clinical application is limited. In response, we constructed a γ3 peptide-decorated and ROS-responsive nanoparticle system encapsulating therapeutic dexamethasone (Dex/PSB-γ3 NPs). In vitro, Dex/PSB-γ3 NPs had rapid H2O2 responsiveness, low cytotoxicity, and strong intracellular ROS removal capacity. In a mouse model of ALI, Dex/PSB-γ3 NPs accumulated at the injured lung rapidly, alleviating pulmonary edema and cytokine levels significantly. The modification of NPs by γ3 peptide achieved highly specific positioning of NPs in the inflammatory area. The ROS-responsive release mechanism ensured the rapid release of therapeutic dexamethasone at the inflammatory site. This combined approach improves treatment accuracy, and drug bioavailability, and effectively inhibits inflammation progression. Our study could effectively reduce the risk of ALI progressing to ARDS and hold potential for the early treatment of ALI.
研究领域:
药理学
·
纳米技术
·
炎症
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 11
·2145
·
IF 7.675
Yuanfang Chen,Yuwei Yang,Haikang Tang,Ziqi Zhang,Xiaoliang Zhou,Wenqing Xu
Radiation exposure can immediately trigger a burst of reactive oxygen species (ROS), which can induce severe cell death and long-term tissue damage. Therefore, instantaneous release of sufficient radioprotective drugs is vital to neutralize those accumulated ROS in IR-exposed areas. To achieve this goal, we designed, synthesized, and evaluated a novel oral ROS-responsive radioprotective compound (M1) with high biocompatibility and efficient ROS-scavenging ability to act as a promising oral drug for radiation protection. The compound is stably present in acidic environments and is hydrolyzed in the intestine to form active molecules rich in thiols. M1 can significantly remove cellular ROS and reduce DNA damage induced by γ-ray radiation. An in vivo experiment showed that oral administration of M1 effectively alleviates acute radiation-induced intestinal injury. Immunohistochemical staining showed that M1 improved cell proliferation, reduced cell apoptosis, and enhanced the epithelial integrity of intestinal crypts. This study provides a promising oral ROS-sensitive agent for acute intestinal radiation syndrome.Keywords:ROS response;aminothiols;oral administration;radioprotection;intestinal damage
研究领域:
药理学
·
放射生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Xinyao Zheng,Shaohui Deng,Yuan Li,Zhipeng Luo,Ziqi Gan,Zhaoping Zheng,Rui Xu,Shan Xiao,Yuxiong Cai,Jianfu Meng,Li Li,Changxing Li,Xiaowen Xue,Wei Dai,Si Qin,Mengying Wang,Kang Zeng,Zecong Xiao,Laixin Xia
Chronic diabetic wounds are a prevalent and severe complication of diabetes, contributing to higher rates of limb amputations and mortality. N6-methyladenosine (m 6 A) is a common RNA modification that has been shown to regulate tissue repair and regeneration. However, whether targeting m 6 A could effectively improve chronic diabetic wound healing remains largely unknown. Here, we found a significant reduction in mRNA m 6 A methylation levels within human diabetic foot ulcers, and the expression level of fat mass and obesity-associated protein (FTO) was significantly increased. We identified that m 6 A modifies the RNA of matrix Metalloproteinase 9 (MMP9), a key factor in diabetic wound healing, to regulate its expression. Importantly, we developed a ROS-scavenging nanocolloidal hydrogel loaded with an FTO inhibitor to increase the m 6 A level of MMP9 RNA in wounds. The hydrogel can effectively accelerate wound healing and skin appendage regeneration in streptozotocin-induced type I diabetic rats at day 14 (approximately 98% compared to 76.98% in the control group) and type II diabetic db/db mice at day 20 (approximately 93% compared to 60% in the control group). Overall, our findings indicate that targeting m 6 A with ROS-scavenging hydrogel loaded with FTO inhibitor may be an effective therapeutic strategy for diabetic wound healing.
研究领域:
分子生物学
·
再生医学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Non-coding RNA Research
·
2025
·
IF 4.7
Ying Wen,Yitong Li,Danhua Zhang,Ziru Liu,Hong Liu,Xiejia Li,Wei Wu,Liyun Zeng,Qiongyan Zou,Wenjun Yi
The prevalence of secondary hyperparathyroidism (SHPT) in advanced chronic kidney disease (CKD) exceeds 80%. Our previous study indicated that photodynamic therapy (PDT) has potential for treating SHPT. Long noncoding RNA (lncRNA) is involved in various oxidative stress and apoptotic processes, but the molecular mechanism remains unreported. In this study, we found that PDT induced apoptosis in SHPT through reactive oxygen species (ROS) accumulation. The expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and heme oxygenase 1 (HO-1) within SHPT was upregulated after PDT. Inhibition of MALAT1 increased PDT-induced ROS, which promoted the apoptosis. Pearson correlation analysis confirmed that there was a positive correlation between MALAT1 and HO-1, and MALAT1 inhibition down-regulated HO-1, whereas concomitant overexpression of HO-1 was able to eliminate the PDT-induced ROS and inhibit apoptosis. The direct binding of MALAT1 to Kelch-like ECH-associated protein 1 (Keap1) protein was confirmed by high-throughput sequencing, RNA pulldown, silver staining and western blotting assays. Si-Keap1 was able to rescue the down-regulation of HO-1 caused by MALAT1 inhibition, restoring the elimination of ROS by HO-1 and attenuating the effect of PDT. In addition, PDT effectively reduced parathyroid hormone (PTH) secretion in SHPT rats, and this effect was further enhanced in combination with MALAT1 inhibitors. Overall, MALAT1 activates downstream HO-1 expression by binding to Keap1, thereby reducing ROS and inhibiting apoptosis, which in turn mediates PDT resistance in SHPT. Inhibition of MALAT1 significantly enhanced the efficacy of PDT, suggesting a potential therapeutic target for improving PDT for SHPT outcomes.
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yifan Li,Qiangwei Liang,Liyue Zhou,Yongjing Cao,Jiayu Yang,Juan Li,Jinxia Liu,Jiawei Bi,Yanhua Liu
The signaling cascade between nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1α (HIF-1α) can be activated by proinflammatory M1 macrophages in rheumatoid arthritis (RA), which produces reactive oxygen species (ROS) and enhances M1 macrophage polarization, thus aggravating the development of RA. Therefore, an ROS-responsive artesunate prodrug micellar nanosystem for co-delivery of dexamethasone (DEX/HA-TK-ART micelles , abbreviated as DEX/HTA) was developed for synergistic inhibition of the HIF-1α/NF-κB cascade to regulate ROS scavenging and macrophage repolarization in RA combination therapy. DEX/HTA micelles displayed prolonged circulation in blood and efficiently co-delivered ART&DEX in the inflamed joints of adjuvant-induced arthritis (AIA) rats; moreover, they were specifically recognized and internalized into M1 macrophages through CD44 receptor-mediated endocytosis . ROS-responsive co-released ART&DEX then exerted a synergistic action to efficiently perform ROS scavenging and repolarization of M1 to M2 macrophages by inhibition of the HIF-1α/NF-κB cascade. The intravenous administration of DEX/HTA micelles into AIA rat models significantly alleviated inflammatory cell infiltration and repaired cartilage injury in the joint. Collectively, our study highlights the therapeutic potential of DEX/HTA micelles for treating RA through synergistic inhibition of the HIF-1α/NF-κB signaling cascade to regulate ROS scavenging and macrophage repolarization. Statement of significance An ROS-responsive artesunate (ART) prodrug micellar nanosystem for co-delivering dexamethasone (DEX), abbreviated as DEX/HA-TK-ART micelle, was developed for synergistic cascade regulation of the HIF-1α/NF-κB pathway on ROS scavenging and macrophage repolarization in combination therapy for rheumatoid arthritis. The well-designed nanosystem showed prolonged circulation in blood and superior ART&DEX accumulation in the inflamed joints of AIA rats; moreover, the micelles were specifically internalized into M1 macrophages and co-released ART&DEX, subsequently leading to inhibition of the HIF-1α/NF-κB pathway for ROS scavenging and macrophage repolarization, thus generating synergistic anti-inflammatory effects in RAW 264.7 cells and AIA rats. The HIF-1α/NF-κB cascade regulation on ROS scavenging and macrophage repolarization based on ART&DEX combination with smart nanotechnology could serve as a promising approach for rheumatoid arthritis therapy.
研究领域:
药理学
·
纳米技术
·
炎症
·
风湿病学
·
药物递送系统
✓ 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）