INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Yushun Chang,Jie Lin,Bo Yang,Yuxuan Shen,Weijun Zhao,Hao Shen,Quan Yang,Haowen Lu,Xiujun Cai,Yifan Wang,Wen Hua
Background Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, exhibits anticancer activity in several malignancies, but its efficacy and mechanisms in gallbladder cancer (GBC) remain undefined. Methods Human GBC cell lines (GBCs) were treated with ALO and assessed for viability, colony formation, 5-Ethynyl-2′-deoxyuridine (EdU) incorporation and apoptosis. Autophagic flux and related signaling were evaluated by western blotting and immunofluorescence. In vivo antitumor activity was determined in a nude mouse xenograft model. Results ALO markedly inhibited the proliferation ability of GBCs and disrupted autophagosome–lysosome fusion, leading to reactive oxygen species (ROS) accumulation and apoptosis. Furthermore, ALO induced DNA damage and nuclear release of double-stranded DNA (dsDNA) to cytoplasm, leading to cyclic-GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING)-mediated interferon (IFN) pathway activation and enhancing natural killer cells (NK cells) activation in vitro. In vivo, ALO reduced subcutaneous GBCs xenograft volume and weight and, along with increased cleaved caspase-3 and BAX expression in tumor tissues, confirming tumor cell apoptosis. Conclusions These findings indicate that ALO may serve as a novel therapeutic candidate for gallbladder cancer by inhibiting autophagic flux to induce ROS-mediated apoptosis while activating the cGAS–STING–IFN pathway to enhance antitumor immunity.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
免疫学
·
转化医学
·
细胞信号转导
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yingnan Zhu,Yalan Ji,Fei Li,Wenwen Gao,Xinyu Xiao,Tiantian Xu,Jie Feng,Jiahang Si,Ruikang Zhang,Yuze Dong
Helicobacter pylori ( H. pylori ) infection, affecting more than half of the world's population, remains the primary etiological driver of stomach cancer. The efficacy of standard antibiotic-based quadruple therapy is declining due to the antibiotic resistance. To address this critical challenge, we developed an inflammation-responsive self-cascading reactive oxygen species (ROS) nanogenerator (BiPt@BSA-PpIX@AP) that synergizes nanozyme catalysis and sonodynamic therapy (SDT) for precision H. pylori eradication. Upon ultrasound activation, the system demonstrated dual-modal ROS amplification. BiPt nanozymes catalytically converted endogenous H 2 O 2 to •OH and O 2 , while protoporphyrin (PpIX) generated more 1 O 2 than free PpIX through enhanced sonoluminescence energy transfer. In H. pylori infected mouse model, the BiPt@BSA-PpIX@AP actively targeted submucosa colonized H. pylori owing to metalloproteinases (MMPs)-triggered hydrolysis and protonation effect, and further eradicated H. pylori and its biofilm by producing ROS. Unlike triple therapy, the nanogenerators had negligible side effects on the normal gut microbiota. This microenvironment-driven self-enhancing ROS nanogenerators have great potential for the treatment of H. pylori infection.
研究领域:
纳米医学
·
抗菌治疗
·
活性氧
·
癌症预防
·
胃肠病学
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产品关联
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Hanbin Deng,Shanyu Yang,Huwen Wu,Han Zhou,Peishen Zhang,Shaowen Cheng,Fabiao Yu,Rui Wang
In the complex process of wound healing, real-time and dynamic monitoring of key indicators such as pH and reactive oxygen species (ROS) in the microenvironment can effectively evaluate the inflammatory status and therapeutic effect of the wound. In this study, a dual-responsive surface-enhanced Raman scattering (SERS) probe was developed, which could simultaneously detect the changes of pH and ROS levels during the wound healing process. The gold–silver core–shell nanoparticles (Au@Ag NPs) were utilized as the active substrate, and 4-mercaptobenzoic acid (4-MBA) and 2,5-dihydroxythiophenol (DHBT) were modified as Raman reporter molecules, which were further coated with polyethylene glycol and bovine serum albumin to improve the biocompatibility and stability. In the Raman spectra, the peak of DHBT at 876 cm −1 was used to indicate the ROS level, while the intensity ratio at 1360 and 1075 cm −1 (I 1360 /I 1075 ) of 4-MBA reflected the pH change. The SERS probe exhibited good ratiometric response characteristics, high selectivity, and low cytotoxicity. In vitro SERS imaging experiments demonstrated that the probe could dynamically monitor ROS generation and pH changes, while SERS imaging in the mouse wound model further confirmed its ability to monitor pH and ROS in the wound microenvironment in vivo. Histological analysis also verified its biosafety. In summary, the dual-responsive SERS probe designed in this study has potential application value in evaluating wound healing effects and provides a new approach for monitoring the wound microenvironment.
研究领域:
生物医学工程
·
纳米技术
·
分析化学
·
伤口护理
·
分子成像
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Bingqing Liang,Fengxian Shi,Can Jin,Min Chen,Yuxiao Niu,Anhong Li,Weihua Xu,Zhongping Ning,Fengfeng Xue,Xinming Li,Yuzhong Yan
Curcumin, a highly hydrophobic phenolic compound, has demonstrated potent anticancer activity. However, poor water solubility and a short biological half-life hinder its clinical application. We developed Curcumin-loaded Pluronic F-127 nanoparticles to enhance the bioavailability of Curcumin. It has been reported that excessive autophagy is considered to be the main mechanism of death of various cancer cells. The aim of this study is to investigate whether the Curcumin-loaded Pluronic F-127 nanoparticles exert anti-colon cancer effects by modulating autophagy and explore the specific regulatory mechanism. The proliferative, migratory and apoptotic activity of CT26 cells was assessed by CCK-8 assay, wound healing assay and flow cytometry, respectively. In addition, levels of reactive oxygen species (ROS) were examined by DCFH-DA assay in vitro. ATP levels were detected by the ELISA. The expression levels of autophagy-related proteins and apoptosis-related proteins were visualized by western blotting. Curcumin-loaded Pluronic F-127 nanoparticle inhibited the proliferation of CT26 cells and the growth of colon tumours by promoting cellular autophagy. In addition, Curcumin-loaded Pluronic F-127 nanoparticle reduced mitochondrial membrane potential and impaired mitochondrial function by increasing ROS levels, disrupting ATP biosynthesis. Then the decreased ATP/AMP ratio activated the AMPK/mTOR/ULK1 autophagy signalling pathway and induced autophagy-dependent apoptosis in CT26 cells. Intriguingly, the apoptosis and excessive autophagy induced by Curcumin-loaded Pluronic F-127 nanoparticle were reversed after pretreatment with the antioxidant N-acetyl-L-cysteine. Curcumin-loaded Pluronic F-127 nanoparticle induced autophagy-dependent apoptosis through ROS-AMPK/mTOR/ULK1 signalling in colon cancer cells. Our study offers new insights for colon cancer treatment advancement.
研究领域:
肿瘤学
·
纳米医学
·
分子生物学
·
药理学
·
细胞信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Chaorong Wei,Lingke Feng,Jing Liu,Mingxia Xu,Yongsheng Cui,Fengyi Lin,Honglian Yu,Zhanzhan Feng,Hong Zhang,Changyang Gong,Peng Mi
X-ray-induced photodynamic therapy (X-PDT) shows significant promise in tumor treatments due to its unlimited tissue penetration but requires delivering sensitizers to tumors. Here, we engineered photosensitizer verteporfin (VP) and T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor OTS964-encapsulated polymeric nanocarriers (VP/OTS964@NPs) for effective tumor X-PDT, molecule-targeted therapy and inducing robust antitumor immunity for synergistic immunotherapy of low immunogenic breast tumors and their lung metastases when combined with PD-L1 blockade. The VP/OTS964@NPs are monodisperse and can be disassembled to release drugs in response to high reactive oxygen species (ROS) levels in the tumor microenvironment or generated during X-PDT. It can efficiently deliver drugs into the TOPK-high expression breast cancer cells, generate ROS and induce ICD effects. By i.v. injection, VP/OTS964@NPs efficiently accumulated in the breast tumors and effectively eradicated tumors upon X-PDT. Additionally, the VP/OTS964@NPs activated the systemic antitumor immune responses, significantly inhibited the distant breast tumors and the lung metastasis of breast tumors, and enhanced the survival rates in combination with PD-L1 blockade. This study presented a strategy for engineering nanocarriers for synergistic molecular therapy, tumor XDT and immunotherapy. Statement of Significance X-PDT is a promising therapeutic modality for cancer treatment. However, its clinical application is hindered by the limited availability of suitable sensitizers and their insufficient tumor-targeting capability. This work aims to construct ROS-sensitive nanocarriers co-loaded with the photosensitizer verteporfin and the TOPK inhibitor OTS964 to achieve synergistic X-PDT for triple-negative breast cancer. By further activating antitumor immune responses, this strategy is designed to suppress the distant and metastatic breast tumors. Overall, this work provides both a nanodrug platform and a therapeutic strategy for the treatment of poorly immunogenic solid tumors.
研究领域:
纳米医学
·
癌症治疗
·
光动力疗法
·
免疫治疗
·
药物递送系统
·
分子靶向治疗
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Mingxiao Shao,Yan Peng,Liyan Qiu
Oxidative stress-mediated tumor therapy leverages reactive oxygen species (ROS) for cancer treatment, but protective autophagy, a major survival pathway for tumor cells, causes therapy resistance. Herein, a self-amplifying ROS-responsive nanovesicle system (CQ/Cu@CT) is designed to enhance oxidative stress while blocking autophagy. Firstly, amphiphilic oligochitosan derivative COS-PEG2KTA-UB is synthesized, where ROS-responsive thioketal acetal (TA) is introduced in form of cinnamaldehyde (CA) prodrug. This polymer self-assembles into nanovesicles, integrating chloroquine (CQ) and supplemental TA to immobilize Cu 2+ via carboxylic coordination. Intracellular ROS triggers nanovesicle dissociation to release CA, Cu 2+ , and CQ. CA induces mitochondrial dysfunction and ROS burst, while Cu 2+ depletes glutathione and generates Cu + for Fenton-like reactions to produce hydroxyl radicals. Meanwhile, due to the inhibition effect of CQ on protective autophagy, CQ/Cu@CT produces significantly high ROS level. The amplified ROS not only aggravates oxidative stress but also accelerates drug release from nanovesicles, which facilitates the drug action against tumors. CQ/Cu@CT also induces immunogenic cell death (ICD) to stimulate dendritic cell maturation and enhance cytotoxic T lymphocyte infiltration. Consequently, CQ/Cu@CT inhibits tumor growth by 67.8 % in a subcutaneous 4 T1 tumor model. This study provides a potent strategy to enhance oxidative stress-based cancer therapy.
研究领域:
纳米医学
·
肿瘤治疗
·
活性氧（ROS）
·
药物递送
·
自噬
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Zhiwei Gao,Mengxue Mo,Qianyue Liu,Jiaxiao Li,Hongshuai Zheng,Yaohui Huang,Yan Liu,Jing Qian,Xuzhi Liang,Yuting Xiao,Yan Long,Chen Qian,Chaoyu Huang,Minghe Jiang,Faquan Lin,Ming Gao,Lin Liao
Acute lung injury (ALI) is a serious lung disease typically caused by excessive inflammatory reactions in the lung. This study aimed to reprogram the lung redox homeostasis for ALI immunotherapy. To address this, a novel polydopamine (PDA) coated black phosphorus nanocarrier (BP@P + MP) was prepared through π-π conjugation and hydrogen bonding between methylprednisolone (MP) and PDA. It was found that BP@P + MP possessed excellent reactive oxygen species (ROS) scavenging abilities, and ROS responsiveness to achieve the controllable release of MP. For lipopolysaccharide induced macrophages and ALI rat models, BP@P + MP could effectively lower intracellular ROS levels, decrease iNOS and IL-1β expression levels, promote Arg-1, IL-10 and HSP70 expression levels, induce macrophage M2 polarization and T cells immunoactivation, and inhibit NF-κB pathway. It finally demonstrated the function of reprogramming lung microenvironment, and promoting lung tissue repair to alleviate ALI. Significantly, following aerosol nebulization (AN), BP@P could retain in the lung for 12 h, and gradually be cleared versus time. This work had designed a novel ROS responsive drug carrier for the synergistic ALI immunotherapy, which may serve as a promising therapeutic strategy for other inflammation related diseases.
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产品关联
DOI
高影响因子
INFLAMMATION RESEARCH
·
2014
·Vol. 63
·期 7
·597-608
·
IF 2.143
Pan Xiaolong,Cao Xiang,Li Na,Xu Yimiao,Wu Qiuyue,Bai Jing,Yin Zhimin,Luo Lan,Lan Lei
Objective Forsythin (FOR) is an active ingredient extracted from the fruit of the medicinal plant Forsythia suspensa (Thunb.) Vahl. Here, we investigated the effect of FOR on LPS-induced inflammatory response and the underlying molecular mechanisms in RAW264.7 macrophages. Materials and methods RAW264.7 cells were pre-treated with or without FOR and then stimulated with or without LPS. The productions of TNF-α, IL-1β, IL-6, PGE 2 and NO were determined by ELISA and nitrite analysis, respectively. The expressions of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were measured by Western blotting and RT-PCR analysis. The activations of signaling molecules were detected by Western blotting using phosphorylation specific antibodies. Reactive oxygen species (ROS) production was determined by ROS assay. Results LPS-induced productions of IL-1β, IL-6, TNF-α, NO and PGE 2 were inhibited by FOR in a dose-dependent manner. FOR also suppressed the LPS-elevated expressions of iNOS and COX-2. Further investigations revealed that FOR significantly inhibited the LPS-induced activations of JAK-STATs and p38 MAPKs, but not of IKKα/β in LPS-stimulated RAW264.7 cells. Additionally, FOR interfered with both JAK-STATs and p38 MAPKs signaling pathways to modulate the expressions of IL-1β, IL-6, TNF-α, iNOS and COX-2. Furthermore, FOR reduced the LPS-induced ROS accumulation, validating that FOR serves as an antioxidant. Conclusions Our data suggested that FOR exerts anti-inflammatory action, at least in part, via suppressing LPS-induced activation of JAK-STATs and p38 MAPKs signalings and production of ROS in macrophage cells.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Gao Chengcheng,Sun Xin,Wu Zhipan,Yuan Huahua,Han Haote,Huang Hongliang,Shu Yuhan,Xu Mengting,Gao Ruilan,Li Shouxin,Zhang Jianbin,Tian Jingkui
Introduction: The leaves of Morus alba L is a traditional Chinese medicine widely applied in lung diseases. Moracin N (MAN), a secondary metabolite extracted form the leaves of Morus alba L, is a potent anticancer agent. But its molecular mechanism remains unveiled.Objective: In this study, we aimed to examine the effect of MAN on human lung cancer and reveal the underlying molecular mechanism.Methods: MTT assay was conducted to measure cell viability. Annexin V-FITC/PI staining was used to detect cell apoptosis. Confocal microscope was performed to determine the formation of autophagosomes and autolysosomes. Flow cytometry was performed to quantify cell death. Western blotting was used to determine the related-signaling pathway.Results: In the present study, we demonstrated for the first time that MAN inhibitd cell proliferation and induced cell apoptosis in human non-small-cell lung carcinoma (NSCLC) cells. We found that MAN treatment dysregulated mitochondrial function and led to mitochondrial apoptosis in A549 and PC9 cells. Meanwhile, MAN enhanced autophagy flux by the increase of autophagosome formation, the fusion of autophagsomes and lysosomes and lysosomal function. Moreover, mTOR signaling pathway, a classical pathway regualting autophagy, was inhibited by MAN in a time- and dose-dependent mannner, resulting in autophagy induction. Interestingly, autophagy inhibition by CQ or Atg5 knockdown attenuated cell apoptosis by MAN, indicating that autophagy serves as cell death. Furthermore, autophagy-mediated cell death by MAN can be blocked by reactive oxygen species (ROS) scavenger NAC, indicating that ROS accumulation is the inducing factor of apoptosis and autophagy. In summary, we revealed the molecular mechanism of MAN against lung cancer through apoptosis and autophagy, suggesting that MAN might be a novel therapeutic agent for NSCLC treatment.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·Vol. 15
·期 3
·e00355
·
IF 9.6
Xin Liu,Shaopeng Liu,Bo Ma,Yang Zhang,Qianxiang Meng,Mingyue Chen,Fangye Chen,Miaomiao Tian,Song Liu,Peng Liu,Kaiyong Cai
Photothermal therapy (PTT) in antimicrobial treatment of diabetic wounds faces the challenge of damaging normal tissues with high temperatures. In this study, mesoporous polydopamine (MPDA) as the core, encapsulated by Zeolitic Imidazolate Framework-8 (ZIF-8) shell, and loaded with berberine (BBR) are used to fabricate MPDA@ZIF-8/BBR core–shell nanoparticles (NPs). Then, those NPs are incorporated into hydrogels formed by reacting carboxymethyl chitosan (CMCS) with oxidized hyaluronic acid (OHA) via Schiff base chemistry, creating a photothermal nanocomposite hydrogel capable of scavenging ROS (Gel- MPDA@ZIF-8/BBR). The hydrogel achieves low-temperature PTT antimicrobial activity by controlled degradation under the weak acidic conditions of the bacterial infection microenvironment and simultaneous release of BBR and Zn 2 ⁺, combined with the mild photothermal effect of MPDA. The released BBR synergistically enhances the photothermal effect by inhibiting bacterial community sensing, effectively disintegrating the bacterial biofilm. More importantly, the composite hydrogels showed good biocompatibility, effectively inhibited the wound inflammatory response, and significantly accelerated wound healing, which achieved low-temperature PTT antibacterial therapy and has the potential to treat diabetic-infected chronic wounds.
研究领域:
生物医学工程
·
伤口愈合
·
纳米医学
·
抗菌治疗
·
糖尿病并发症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2025
·
IF 10.9
Pengchen Wang,Jintong Na,Xiyu Liu,Minhui Cui,Ganghao Liang,Xinyue He,Haihua Xiao,Yongxiang Zhao,Yuan Liao,Liping Zhong
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by low immune response rates and high recurrence. This underscores an urgent need for more effective treatment strategies for liver cancer patients. Ferroptosis, a type of cell death associated with iron-dependent lipid peroxidation, has shown significant potential in HCC treatment. However, the efficacy of this monotherapy for tumor treatment remains limited. Enhancing reactive oxygen species (ROS) accumulation and lipid peroxide formation by inhibiting the tumor cell antioxidant system has emerged as a promising anti-tumor strategy. In this study, we developed a nanoplatform, NP (nanoparticle)-BSD@WFR, specifically tailored for HCC treatment. This system combines a biodegradable sonodynamic polymer (BSD) with warfarin (WFR), a VKORC1L1 inhibitor that prevents intracellular peroxide elimination and enhances ferroptosis. Under ultrasound irradiation, NP-BSD@WFR generates ROS and releases WFR, directly targeting cancer cells. Concurrently, ROS and WFR synergistically enhance lipid peroxide production in cancer cells, triggering ferroptosis and activating the immune system. Animal studies further demonstrate that combining sonodynamic therapy with WFR-induced ferroptosis produces a synergistic anti-tumor effect, promoting a strong immune response in vivo. This study introduces an innovative therapeutic approach combining sonodynamic therapy and WFR for HCC treatment and highlights its promising efficacy.
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Maohua Chen,Menghuan Li,Yujia Wei,Chencheng Xue,Maowen Chen,Yang Fei,Lu Tan,Zhong Luo,Kaiyong Cai,Yan Hu
Bioenergy (ATP) is essentially required for supporting the osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs). However, factors such as high ROS levels and decreased glucose metabolism severely limit the bioenergy production in osteoporotic MSCs . We have prepared CaCO 3 -Quercetin- chromium (CaCO 3 -Qu-Cr) nanoparticles via ion coordination and packaged them into ROS-responsive gelatin/chitosan coating on titanium surface (Ti/Gel/CaCO 3 -Qu-Cr), aiming to improve the ATP production and cell mineralization by ameliorating ROS levels via Qu-mediated antioxidative effect and the promotional effect of Qu-Cr combination on glucose metabolism. Characterization results confirmed that Ti/Gel/CaCO 3 -Qu-Cr could be degraded in an ROS-responsive manner to release CaCO 3 -Qu-Cr nanoparticles continuously and eliminate excessive ROS in both the MSCs and microenvironment . Meanwhile, Ti/Gel/CaCO 3 -Qu-Cr significantly increased the glucose uptake and metabolism in osteoporotic MSCs and boosted their ATP and citrate production. This study laid the foundation for the development of functional titanium-based implants for the improvement of osteoporotic osseointegration .
研究领域:
生物材料
·
组织工程
·
骨科
·
纳米技术
·
干细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）