ACS Applied Nano Materials
·
2024
·
IF 5.3
Cijun Shuai,Jiachi Zhao,Qi Zhong,Shuping Peng,Jun Zan,Zhen Cao
Although photothermal therapy is widely employed for tumor treatment because of its high tumor cell selectivity and low apoptosis resistance, heat-shock proteins (HSPs) impart resistance to heat-induced apoptosis in tumor cells, thus diminishing the therapeutic effectiveness. To this end, tin selenide (SnSe) was grown in situ on reduced graphene oxide (rGO) nanosheets to construct a photothermal–thermoelectric SnSe/rGO nanosystem. The rGO component converted near-infrared light energy into localized thermal energy, resulting in the thermal ablation of tumor cells. Meanwhile, SnSe converted temperature fluctuations into pyroelectric charges, which interacted with surrounding O2 molecules to generate reactive oxygen species that oxidized the amino acids on the HSPs, which changed the protein conformation and functionally damaged the tumor cells. In addition, rGO functioned as an efficient electron acceptor to increase electron mobility, thus enhancing the thermoelectric conversion efficiency of SnSe. Then, the SnSe/rGO nanosystem was incorporated into a poly-l-lactic acid bone scaffold to prevent tumor recurrence. Results showed that the composite scaffold not only exhibited good photothermal and thermoelectric effects. In vitro cell tests demonstrated that the scaffold generated 1O2 based on temperature fluctuations and the antitumor rate reached 86.6% against osteosarcoma MG-63 cells.
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DOI
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 51
·29711-29720
·
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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高影响因子
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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高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 15
·3401-3411
·
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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TOXICOLOGY
·
2022
·
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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高影响因子
ACS Applied Materials & Interfaces
·
2022
·
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
·
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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高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
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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高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Kai Dong,Qiuya Lei,Runhao Guo,Xianglong Wu,Yanni Zhang,Ning Cui,Jian-Yu Shi,Tingli Lu
Purpose: The levels of reactive oxygen species (ROS) in tumor cells are much higher than that in normal cells, and rise rapidly under the influence of exogenous or endogenous inducing factors, eventually leading to the apoptosis of tumor cells. Therefore, this study prepared a dual pH/reducing-responsive poly (N-isopropylacrylamide-co-Cinnamaldehyde-co-D-α-tocopheryl polyethylene glycol 1000 succinate, PssNCT) nanogels, which employed two exogenous ROS inducers, cinnamaldehyde (CA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), to selectively induce apoptosis by regulating ROS levels in tumor cells.Methods: The PssNCT nanogels were prepared by the free radical precipitation polymerization under the crosslink between pH-sensitive hydrazone and reducing-sensitive disulfide bonds, followed by the physicochemical and morphological characteristics investigations. Plasma stability, dual pH/reducing responsive degradation and in vitro release were also assessed. In cell experiments, cytotoxicity in different cells were first detected. The intracellular ROS levels and mitochondrial functions of tumor cells were then evaluated. Moreover, the apoptosis and western-blot assays were employed to verify the association between ROS levels elevation and apoptosis in tumor cells.Results: The nanogels exhibited a round-like hollow structure with the diameter smaller than 200nm. The nanogels were stable in plasma, while showed rapid degradation in acidic and reducing environments, thus achieving significant release of CA and TPGS in these media. Furthermore, the sufficient amplification of ROS signals was induced by the synergistically function of CA and TPGS on mitochondria, which resulted in the opening of the mitochondrial apoptotic pathway and enhanced cytotoxicity on MCF-7 cells. However, nanogels barely affected L929 cells owing to their lower intracellular ROS basal levels.Conclusion: The specific ROS regulation method achieved by these nanogels could be explored to selectively kill tumor cells according to the difference of ROS signals in different kinds of cells.
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高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2021
·
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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高影响因子
BIOMATERIALS
·
2022
·
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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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 .
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高影响因子
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