CHEMICAL ENGINEERING JOURNAL
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2025
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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.
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CARBOHYDRATE POLYMERS
·
2025
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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.
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高影响因子
Acta Biomaterialia
·
2025
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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.
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BIOORGANIC CHEMISTRY
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2025
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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.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2024
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IF 8
Xiaoyan Huang,Wanlu Sun,Yanyan Zhu,Chao Zhao,Baojin Tan,Hai-Yan Wang,Yi Liu
Photodynamic therapy (PDT) could induce apoptosis by releasing reactive oxygen species (ROS) to treat tumor. Application of pH/light dual-activated nanoparticles could generate ROS in the acidic tumor microenvironment under 808 nm laser irradiation for precise treatment. L-arginine (L-Arg) triggered by ROS is an efficient nitric oxide (NO) donor for gas therapy. In addition, it is reported that peroxynitrite (ONOO - ) produced by rapid reaction of ROS and NO could sensitize PDT and induce apoptosis for synergistic treatment. Herein, we developed the L-Arg loaded pH/light dual-activated PEGylated photosensitizer for self-assembly into nanoparticles named Rho-Arg. As measured by fluorescence spectroscopy, the pKa of Rho-Arg was 5.5, which is suitable for applying in the tumor microenvironment. The nanoplatform was firstly activated under the acidic condition of tumor, and then illuminated by 808 nm laser to controllably release ROS, and sequentially produced NO and ONOO - . In conclusion, the Rho-Arg nanoplatform may provide a promising synergistic therapy tool for tumor treatment.
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CURRENT MEDICINAL CHEMISTRY
·
2024
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IF 3.5
Gan Xin,Xie Jingwen,Dong Zhaojun,Wu Yuna,Zeng Xiaoqing,Yang Zhenzhen,Liu Bo,Zhu Min,Wang Bozhen,Li Wulan,Wang Ledan,Zhang Huajie,Wu Jianzhang,Hu Yue
Background: Pyroptosis, a cell death process triggered by chemotherapy drugs, has
emerged as a highly promising mechanism for combating tumors in recent years. As the lead of
new drugs, natural products play an important role in the discovery of anticancer drugs. Compared
to other natural products, the medicine food homologous natural products (MFHNP) exhibit a superior
safety profile. Among a series of MFHNP molecular skeletons, this study found that only
benzylideneacetophenone (1) could induce cancer cell pyroptosis. However, the anti-cancer activity
of 1 remains to be improved.
Aims: This study aimed to find a pyroptosis inducer with highly effective antitumor activity by
modifying the chalcone structure.
Methods: To examine the effect of the Michael receptor in compound 1 on the induction of pyroptosis,
several analogs were synthesized by modifying the Michael acceptor. Subsequently, the anticancer
activity was tested by MTT assay, and morphological indications of pyroptosis were observed
in human lung carcinoma NCI-H460 and human ovarian cancer CP-70 cell lines. Furthermore,
to improve the activity of the chalcone skeleton, the anticancer group 3,4,5-
trimethoxyphenyl was incorporated into the phenyl ring. Subsequently, compounds 2-22 were designed,
synthesized, and screened in human lung cancer cells (NCI-H460, H1975, and A549). Additionally,
a quantitative structure-activity relationship (QSAR) model was established using the
eXtreme Gradient Boosting (XGBoost) machine learning library to identify the pharmacophore.
Furthermore, both in vitro and in vivo experiments were conducted to investigate the molecular
mechanisms of pyroptosis induced by the active compound.
Results: α, β-unsaturated ketone was the functional group of the chalcone skeleton and played a
pivotal role in inducing cancer cell pyroptosis. QSAR models showed that the regression coefficients
(R2) were 0.992 (A549 cells), 0.990 (NCI-H460 cells), and 0.998 (H1975 cells). Among these
compounds, compound 7 was selected to be the active compound. Moreover, compound 7 was
found to induce pyroptosis in lung cancer cells by upregulating the expression of CHOP by increasing
the ROS level. Furthermore, it effectively suppressed the growth of lung cancer xenograft
tumors.
Conclusion: Compound 7 exhibits antineoplastic activity by regulating the ROS/ER stress/pyroptosis
axis and is a kind of promising pyroptosis inducer.
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高影响因子
Advanced Science
·
2023
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IF 15.1
Huiyun Li,Yusong Yuan,Lingpu Zhang,Chun Xu,Hailin Xu,Zhiwei Chen
Osteoarthritis (OA) is a chronic joint disease characterized by synovitis and joint cartilage destruction. The severity of OA is highly associated with the imbalance between M1 and M2 synovial macrophages. In this study, a novel strategy is designed to modulate macrophage polarization by reducing intracellular reactive oxygen species (ROS) levels and regulating mitochondrial function. A ROS-responsive polymer is synthesized to self-assemble with astaxanthin and autophagy activator rapamycin to form nanoparticles (NP@Poly RHAPM ). In vitro experiments show that NP@Poly RHAPM significantly reduced intracellular ROS levels. Furthermore, NP@Poly RHAPM restored mitochondrial membrane potential, increased glutathione (GSH) levels, and promoted intracellular autophagy, hence successfully repolarizing M1 macrophages into the M2 phenotype. This repolarization enhanced chondrocyte proliferation and vitality while inhibiting apoptosis. In vivo experiments utilizing an anterior cruciate ligament transection (ACLT)-induced OA mouse model revealed the anti-inflammatory and cartilage-protective effects of NP@Poly RHAPM , effectively mitigating OA progression. Consequently, the findings suggest that intra-articular delivery of ROS-responsive nanocarrier systems holds significant promise as a potential and effective therapeutic strategy for OA treatment.
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CARBOHYDRATE POLYMERS
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2020
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IF 7.182
Jin Wang,Lehao Zhou,Qihao Sun,Haibo Cai,Wen-Song Tan
The proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) needed to be promoted for their use in stem cell-based therapy for large bone defects. This study aimed to prepare porous 2a-2 g scaffolds with antioxidant activity to reduce intracellular reactive oxygen species (ROS), which resulted in promoting the proliferation and osteogenic differentiation of MSCs. A series of novel chemically modified 2a-2 g scaffolds were fabricated by an acid-soluble/alkali-insoluble method. Besides, these 2a-2 g scaffolds had good biocompatibility, physicochemical properties and the ability to promote osteogenic differentiation of human adipose-derived stem cells ( h ADSCs). However, the proliferation ability of h ADSCs on 2a-2f scaffolds was weakened. Interestingly, 2 g scaffold had a positive effect on h ADSCs proliferation. These results indicated that the reduction of intracellular ROS was not conducive to h ADSCs proliferation but beneficial to h ADSCs osteogenic differentiation. Taken together, these significant results highlighted potential therapeutic benefit of 2 g scaffold in large bone defects.
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REPRODUCTIVE TOXICOLOGY
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2021
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IF 3.143
Yingying Zhang,Jiaqi Tang,Na Li,Jianying Tao,Yan Zhang,Yumeng Zhang,Yang Ye,Qiutong Zheng,Ting Xu,Yanping Liu,Pengjie Zhang,Lingjun Li,Huan Li,Yun He,Hongyu Su,Qinyuan He,Miao Sun,Zhice Xu
Pulmonary arterial hypertension is a progressive disorder characterized by remodeling and increased small pulmonary arteries resistance. Endothelin-1 (ET-1) was related to PAH and ET-1 receptors were up-regulated selectively in the lung when exposed to toxic factor hypoxia. However, the role of ET-1 signaling in the pathogenesis of prenatal hypoxia-induced pulmonary abnormalities remains to be elucidated. Pregnant rats were divided into prenatal hypoxia (10.5 % O 2 from gestational day 4–21) and control group. Their three-month-old offspring male rats were tested for vascular functions and molecular analysis, DNA methylation was assessed for cellular hypoxia. Functional testing showed that ET-1-mediated vasoconstriction was enhanced, and the expressions of endothelin A receptor/B receptor (ET A R/ET B R), inositol 1,4,5-trisphosphate receptor, type 1, and the sensitivity of calcium channels were increased in the small pulmonary arteries following prenatal hypoxia. q-PCR and DHE staining showed that the expressions of NADPH oxidase 1/4 (Nox1/4) were up-regulated, along with the increased production of superoxide anion. Furthermore, superoxide anion promoted ET-1-mediated pulmonary artery contraction. In the pulmonary artery smooth muscle cell experiments, q-PCR, Western Blot, CCK8 and DHE staining showed that the expressions of ET B R, Nox1/4, and superoxide anion were increased by hypoxia, along with promoted cell proliferation. 2,2,6,6-Tetramethyl-1-piperidinyloxy reversed hypoxia-induced cell proliferation. ET B R antagonist BQ788 inhibited hypoxia-increased expressions of Nox1/4, superoxide anion production, and proliferation of cells. Moreover, methylation analysis indicated that hypoxia decreased the methylation levels of the ET B R promoter in the pulmonary artery smooth muscle cells. The results indicated that prenatal toxic factor hypoxia resulted in abnormal ET B R activation, which enhanced ET-1-mediated vasoconstriction of pulmonary arteries and pulmonary artery smooth muscle cell proliferation through ET B R/Nox1/4-derived ROS pathway.
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BIOMATERIALS
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2022
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IF 15.304
Xuan Li,Kun Xu,Ye He,Bailong Tao,Ke Li,Chuanchuan Lin,Jingwei Hu,Jing Wu,Yi Wu,Shaopeng Liu,Peng Liu,Huaiyu Wang,Kaiyong Cai
Ideal titanium implants are required to participate in bone repair actively to improve in situ osteointegration. However, the traditional surface functionalization methods of titanium implants are difficult to both achieve the active regulation and long-term stability of bioactive components. Here, a novel functionalized titanium which loaded with thymosin β4 (Tβ4) and covered by a hydrogel coating was designed and evaluated. A strong adhesion between the coating and the titanium substrate was realized by the synergistic action of borate ester bonds and surface topological structure. The hydrogel coating also achieved an in vivo adhesion between implant and tissue through hydrogen bonds and borate bonds. In addition, based on the ROS response property of borate bonds, the implant can release Tβ4 in response to the immune reaction of bone healing by regulating the polarization of macrophages, thereby reducing the fibrosis formation around the implant interface and promoting vascularization and osteointegration of bone defects.
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JOURNAL OF BIOLOGICAL CHEMISTRY
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2021
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IF 5.157
Lei Chen,Miao Hao,Jingmin Yan,Lin Sun,Guihua Tai,Hairong Cheng,Yifa Zhou
Heat-modified citrus pectin, a water-soluble indigestible polysaccharide fiber derived from citrus fruits and modified by temperature treatment, has been reported to exhibit anticancer effects. However, the bioactive fractions and their mechanisms remain unclear. In this current study, we isolated an active compound, trans-4,5-dihydroxy-2-cyclopentene-l-one (DHCP), from heat-treated citrus pectin, and found that is induces cell death in colon cancer cells via induction of mitochondrial ROS. On the molecular level, DHCP triggers ROS production by inhibiting the activity of succinate ubiquinone reductase (SQR) in mitochondrial complex II. Furthermore, cytotoxicity, apoptotic activity, and activation of caspase cascades were determined in HCT116 and HT-29 cell-based systems, the results indicated that DHCP enhances the sensitivity of cancer cells to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), with DHCP-induced ROS accounting for the synergistic effect between DHCP and TRAIL. Furthermore, the combination of DHCP and TRAIL inhibits the growth of HCT116 and HT-29 xenografts synergistically. ROS significantly increases the expression of TRAIL death receptor 5 (DR5) via the p53 and C/EBP homologous protein pathways. Collectively, our findings indicate that DHCP has a favorable toxicity profile and is a new TRAIL sensitizer that shows promise in the development of pectin-based pharmaceuticals, nutraceuticals, and dietary agents aimed at combating human colon cancer.
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CHEMICAL ENGINEERING JOURNAL
·
2025
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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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