Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Yanjuan Huang,Tao Zhang,Qin Wei,Zishan Zeng,Yujun Gong,Xiaoyu Xu,Meixu Chen,Chunshun Zhao
Posterior capsular opacification (PCO) is the leading cause of vision loss after cataract, mainly caused by the adhesion, proliferation and trans-differentiation of post-operative residual lens epithelial cells (LECs). Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades. Herein, we developed a “NIR-triggered ROS storage” intraocular implant (CTR-Py-PpIX) based on capsular tension ring (CTR), which is concurrently linked with photosensitizer protophorphyrin IX (PpIX) and energy storage 2-pyridone derivative (Py), to guarantee instantaneous and sustainable ROS generation for LECs killing, aiming to achieve more efficient and safer photodynamic therapy (PDT) to effectively prevent PCO. The silylated PpIX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-PpIX. Results demonstrated that CTR-Py-PpIX had dual functions of PDT and battery, in which PpIX could generate ROS extracellularly under irradiation, with one part directly inhibiting LECs by lipid peroxidation (LPO) induction of cell membranes. Meanwhile, the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed. Ultimately, the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions, achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility. This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.
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ACS Applied Materials & Interfaces
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2022
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IF 10.383
Runze Zhao,Xiaoyue Ning,Mengqi Wang,Huanhuan Wang,Guang Xing,Li Wang,Chengzhi Lu,Ao Yu,Yongjian Wang
Nanoprodrugs with responsive release properties integrate the advantages of stimuli-responsive prodrugs and nanotechnology. They would provide ultimate opportunity in fighting atherosclerosis. In this study, we synthesized a redox-responsive nanoprodrug of simvastatin (TPTS) by conjugating α-tocopherol polyethylene glycol derivative to the pharmacophore of simvastatin with a thioketal linker. TPTS formed nanoparticles and released parent simvastatin in the presence of hydrogen peroxide. Moreover, by taking advantage of the self-assembly behavior of TPTS, we developed a fibronectin-targeted delivery system (TPTS/C/T) to codelivery simvastatin prodrug and ticagrelor. In vitro and in vivo experiments indicated that TPTS and TPTS/C/T had good stability, which could reduce off-target leakage of drugs. They greatly inhibited the M1-type polarization of macrophages; reduced intracellular reactive oxygen species level and inflammatory cytokine; and TNF-α, MCP-1, and IL-1β were secreted by macrophage cells, thus providing enhanced anti-inflammatory and antioxidant effects compared with free simvastatin. TPTS/C/T realized targeted drug release to plaques and synergistic therapeutic effects of simvastatin and ticagrelor on atherosclerosis treatment in an ApoE–/– mouse model, resulting in excellent atherosclerosis therapeutic efficacy and a promising biosafety profile. Therefore, this study provides a new method for manufacturing statin nanodrugs and a new design idea for related responsive drug release nanosystems for atherosclerosis.
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高影响因子
Advanced Science
·
2020
·Vol. 7
·期 20
·2001853
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IF 15.84
Ying Hao,Yuwen Chen,Xinlong He,Yongyang Yu,Ruxia Han,Yang Li,Chengli Yang,Danrong Hu,Zhiyong Qian
The combination of chemotherapy and photodynamic therapy (PDT) has promising potential in the synergistic treatment of cancer. However, chemotherapy and photodynamic synergistic therapy are impeded by uncontrolled chemotherapeutics release behavior, targeting deficiencies, and hypoxia-associated poor PDT efficacy in solid tumors. Here, a platinum nanozyme (PtNP) loaded reactive oxygen species (ROS)-responsive prodrug nanoparticle (CPT-TK-HPPH/Pt NP) is created to overcome these limitations. The ROS-responsive prodrug consists of a thioketal bond linked with camptothecin (CPT) and photosensitizer-2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH). The PtNP in CPT-TK-HPPH/Pt NP can efficiently catalyze the decomposition of hydrogen peroxide (H 2 O 2 ) into oxygen to relieve hypoxia. The production of oxygen can satisfy the consumption of HPPH under 660 nm laser irradiation to attain the on-demand release of CPT and ensure enhanced photodynamic therapy. As a tumor diagnosis agent, the results of photoacoustic imaging and fluorescence imaging for CPT-TK-HPPH/Pt NP exhibit desirable long circulation and enhanced in vivo targeting. CPT-TK-HPPH/Pt NPs effectively inhibit tumor proliferation and growth in vitro and in vivo. CPT-TK-HPPH/Pt NP, with its excellent ROS-responsive drug release behavior and enhanced PDT efficiency can serve as a new cancer theranostic agent, and will further promote the research of chemophotodynamic synergistic cancer therapy.
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RSC Advances
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2019
·Vol. 9
·期 51
·29711-29720
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IF 3.049
Yan Zhang,Yunyun Wang,Yuxun Zhao,Wen Gu,Yongqiang Zhu,Shifa Wang
A series of novel camphor-based pyrimidine derivatives (3a–3x) have been synthesized; their structures were determined by using conventional methods and compound 3f was further confirmed through single crystal XRD analysis. The cytotoxic activity of the target compounds against a panel of human normal (GES-1) and cancer cell lines (MDA-MB-231, RPMI-8226, A549) was evaluated by MTS assay. Here we found that compound 3f exhibited the strongest anti-tumor activity, comparable to that of etoposide, and had much lower cytotoxicity to normal GES-1 cells (IC50 > 50 μM) than the reference drug (IC50 = 8.89 μM). Subsequent mechanism studies in MDA-MB-231 cells revealed that compound 3f caused G0/G1 phase arrest and apoptosis in a dose dependent manner. Moreover, the loss of mitochondrial membrane potential and enhancement of cellular ROS levels were also observed upon 3f treatment, which indicated that 3f exerted cytotoxic activity by a ROS-mediated mitochondrial apoptosis pathway. This result was confirmed by a significant increase in the expression of pro-apoptotic proteins Bax, cytochrome C and caspase-3, and downregulation of anti-apoptosis protein Bcl-2. Overall, 3f can be adopted for further investigation in the development of antitumor agents based on natural products.
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TOXICOLOGY
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2022
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IF 4.571
Peng Lin,Xu Tong,Fan Xue,Chi Qianru,Tang Xinyu,Li Zhe,Bai Zhikun,Li Shu
Polystyrene nanoplastics (PS NPs) contamination is a serious problem for human and animal health. Excessive exposure to PS NPs can affect the structure and function of the heart. And lipopolysaccharide (LPS) induces myocardial damage , leading to myocardial fibrosis (MF). To investigate whether PS NPs exacerbate LPS-induced myocardial autophagy and fibrosis , we established in vivo and in vitro models of PS NPs/LPS exposure alone and in combination. We found that PS NPs/LPS exposure disrupts myocardial structure, significantly increases reactive oxygen species (ROS), triggers oxidative stress , promotes TGF-β1/Smad pathway activation, and leads to elevated levels of fibrotic proteins and collagen. Meanwhile, activation of AMPK/mTOR/ULK1 signaling pathway induced autophagy onset, and combined exposure of PS NPs/LPS exacerbated MF and autophagy. H9C2 cells were used for in vitro experiments, and the experimental results showed that the addition of TGF-β receptor inhibitor LY2109761 to the exposed group not only inhibited the upregulation of fibrotic genes but also effectively reduced the expression of autophagic signals, indicating that combined exposure of PS NPs and LPS mediates and regulates cardiac autophagy through TGF-β1. The above results suggest that PS NPs exacerbate LPS-induced MF and autophagy in mice via ROS/TGF-β1/Smad. Our study provides some new evidence to clarify the potential mechanisms of PS NPs-induced cardiotoxicity.
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Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 15
·3401-3411
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IF 6.331
Ming Wang,Miao Li,Yunli Wang,Yiran Shao,Yingchun Zhu,Shiping Yang
Hydroxyapatite (HA) has attracted wide attention for medical application due to its biocompatibility and bioactivity. However, the infection problems of HA remain among the leading reasons for implantation failure. Thus, it is urgent to endow HA biomaterials with antibacterial activity. Herein, the high antibacterial activity was achieved by introducing trace Mn3+ and H vacancy couples in HA through a facile heat-treatment strategy in air. The theoretical results indicated that Mn3+ was preferentially substituted for the Ca(2) site in the HA structure with a charge-compensating H vacancy appearing at the adjacent OH− site. The antibacterial tests showed that Mn-HA possessed antibacterial activity towards both E. coli and S. aureus with trace Mn content at the ppm level, and implied that Mn3+ and centers may play an important role in the antibacterial process. The Mn3+ and couples in Mn-HA, serving as oxidative and reductive centers respectively, could then collectively participate in the CoQ/CoQH2 redox cycling and synergistically facilitate the accumulation of CoQ˙− and ROS radicals. This enhanced ROS production was the main factor to endow Mn-HA with efficient antibacterial activity. Moreover, the in vitro bioactivity assay showed that Mn-HA materials exhibited enhanced osteogenic activity and good biocompatibility. Therefore, this work not only provides a feasible method to control the oxidation state of Mn elements in HA, but also proposes a novel trace Mn3+-doped HA for potential applications in tissue engineering.
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Nano Today
·
2025
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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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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
·
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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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.
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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
·
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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